Cho-Kai Wu - Academia.edu (original) (raw)
Papers by Cho-Kai Wu
Acta Cardiologica Sinica, 2017
Drug-eluting stents are widely used in coronary artery intervention. However, vessel caging and v... more Drug-eluting stents are widely used in coronary artery intervention. However, vessel caging and very late thrombotic events are of persistent and substantial concern. Bioresorbable vascular scaffolds (BVS) were developed to deliver vascular reparative therapy, by eliminating permanent mechanical restraint. However, data regarding its clinical performance is lacking. After the BVS implantation procedure received national approval in May 2014, patients receiving BVS implantation until November 2014 in National Taiwan University Hospital (NTUH) were enrolled. Clinical variables, angiographic data, procedural details, and follow-up information were collected and compared with those receiving BVS at NTUH as part of the global ABSORB EXTEND trial. A total of 35 patients (38 target vessels) with 48 BVS implanted after approval were enrolled, as the "real-world practice" group. Data of the 34 patients (34 target vessels) with 37 BVS implanted in the ABSORB EXTEND trial were also o...
Annals of medicine, Jan 7, 2017
Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac... more Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by ISHNE and HRS/EHRA/APHRS were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before. This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria. A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased 71...
Journal of Clinical Lipidology, 2017
Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dial... more Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive protein levels of ≥1.5 mg/L, and LVDD, diagnosed by conventional and tissue Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant improvement of early mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site (Nominal change for E/Emedial: -5.01 ± 6.36 vs 1.80 ± 6.59 for atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SRIVR, 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671).
Clinical Science, 2017
Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries.... more Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies have shown that risk factors for CAE were related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays. Wilcoxon's rank sum tests revealed 89 genes with significantly different methylation levels (P<0.05 and Δβ > |0.1|). Functional characterization using the DAVID database and gene set enrichment analysis indicated that these genes were involved in immune and inflammatory responses. Of these genes 6 were validated in 29 CAE patients and 87 matched individuals with CAE, using pyro-sequencing. TLR6 and NOTCH4 showed significant differences in methylation between the two groups, and lower protein levels of toll-like receptor 6 (TLR6) were detected in CAE patients. In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE.
Acta Cardiologica Sinica, 2013
The objective of this study was to evaluate the renin-angiotensin system genetic effects and phar... more The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients. Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models. Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE in...
Medicine, 2016
Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane pro... more Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505-5.545, P = 0.001; and OR 2.55, 95% CI = 1.428-4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025-3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.
Zhonghua Minguo xin zang xue hui za zhi = Acta Cardiologica Sinica, 2016
The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump... more The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping(TM) (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation o...
Scientific Reports, 2016
Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failu... more Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short-axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age (1.87, 95% CI: 0.61-3.13, p = 0.004) and ECV (3.77, 95% CI: 2.72-4.81, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) were positively associated with Tmv. The results remained robust in certain subgroups. In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is closely related to LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s underlying mechanisms leading to poor prognosis.
Nature communications, Jan 2, 2016
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide as... more Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10(-24)). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor...
PloS one, 2016
Patients with severe kidney function impairment often have autonomic dysfunction, which could be ... more Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. A total of 132 ...
Scientific reports, Jan 19, 2015
Heart failure with preserved ejection fraction (HFPEF) is characterized by myocardial interstitia... more Heart failure with preserved ejection fraction (HFPEF) is characterized by myocardial interstitial fibrosis. A total of 146 patients with HFPEF, were recruited. HFPEF severity was determined using Doppler imaging (E/Em) and also cardiac magnetic resonance imaging (CMRI). Canine modeling of HFPEF was induced by aortic banding. Hemodynamic and echocardiographic data were obtained before and after pressure loading and myocardial Galectin-3 was determined. Mechanical stretch of cultured cardiomyocytes served as the cellular model of HFPEF. Patients with severe HFPEF had significantly higher plasma Galectin-3 levels. Significant correlation between plasma Galectin-3 and E/Em in advanced HFPEF patients was noted. After 2 weeks of pressure overload in canine models, the protein expression of Galectin-3 from LV myocardial tissue was significantly increased (p < 0.01) compared with controls. Galectin-3 expression paralleled the severity of LV diastolic dysfunction by evaluation of CMRI (r...
The Journal of clinical endocrinology and metabolism, Jan 24, 2015
The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to... more The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum ATPase (SERCA). Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and 3 patients with idiopathic hyperaldosteronism), and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation (F/NMD) were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells (HAOSMCs) Setting: Academic clinical research center Participants: Thirty-five patients with PA...
International Journal of Cardiology, 2015
Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation ... more Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation (AF) in dialysis patients is unclear. We used a database from the Registry for Catastrophic Illness from the National Health Research Institute. All dialysis patients aged 18 or older without history of AF before ESRD were incorporated. A total of 113,191 dialysis patients were enrolled in the study. The median follow-up time was 4.17years. We collected information on prescribed drug dosage, number of days of treatment and the total number of pills dispensed from the outpatient pharmacy prescription database. All individuals in the study cohort with the first occurrence of AF were included as cases. In spironolactone group, the incidence of developing new AF was significantly lower than that in the control group both before (0.8% vs. 3.3%, P=0.019) and after PS matching (1.2% vs. 3.0%, P=0.019). Before PS matching, Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression analyses showed that spironolactone was associated with 60% reduction of new AF (HR=0.372 [0.200-0.692], P=0.002) and the protective effect is dose-responsive in accumulated dose, treatment duration and mean daily dose. After PS matching, the overall AF prevention effect remained significant (HR=0.400 [0.179-0.895], P=0.026) while the dose-response relationship became borderline significant. Subgroup analyses showed that the protective effect was more evident in some specific subgroup patients. Our study showed that spironolactone therapy was associated with lower risk of developing AF in a dose-responsive manner in patients with dialysis. Further randomized study is needed to confirm this observation.
Atherosclerosis, 2015
Pericardial fat (PF) has been hypothesized to exert local pathogenic effects on nearby cardiac st... more Pericardial fat (PF) has been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity which might be associated with the presence of arrhythmia or even worse outcomes. The aims of this study was to characterize the relationship between PF and the prognosis in patients with systolic heart failure (HF). This is a retrospective cohort study of a cardiac magnetic resonance imaging (CMRI) database from 2004 to 2011. Fifty patients with systolic HF underwent CMRI examinations were included. We also enrolled twenty patients with HF as the control group. The cine imaging was analyzed to derive total PF volumes, left ventricular volumes and mass and left ventricular ejection fraction by using a previously validated technique. The outcomes, including ventricular tachycardia (VT), ventricular fibrillation (VF) and total mortality were obtained by reviewing medical records. After a median follow-up of 694 days, patients with VT/VF had significant larger indexed PF volumes than those without [36.3 (32.8-43.1) ml/m(2) vs. 24.1 (20.2-27.6) ml/m(2), p = 0.001]. The mortality group also had significant larger indexed PF volumes (PF/body surface area) than those without [31.3 (22.8-38.4) ml/m(2) vs. 23.9 (19.8-27.3) ml/m(2), p = 0.010]. Indexed PF volumes were associated with the development of VT/VF (Hazard ratio, 7.510; 95% C.I, 0.901-62.582, p = 0.062) and mortality (Hazard ratio, 3.998; 95% C.I, 1.077-14.845, p = 0.038) by Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s regression analyses. PF is associated with the development of VT/VF and long-term overall mortality in patients with systolic HF.
Medicine, 2015
Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dial... more Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43-3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45-2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients.
International Journal of Cardiology, 2015
The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in... more The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in dialysis patients. We used a database from the Registry for Catastrophic Illness from the National Health Research Institute (NHRI), which encompasses almost 100% of the patients receiving dialysis started from 1997 to 2008 in Taiwan. All dialysis patients aged 18 or older without history of cardiovascular events in 1997 and 1998 were incorporated. Finally, 113,191 dialysis patients were enrolled. We used propensity score (PS) matching method and Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression models to estimate hazard ratios for AF events for statin users vs. nonusers. In statin group, the incidence of developing new AF was significantly lower than that in control group (1.1% vs. 3.8%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The PS-based selection process identified 2146 patients receiving statins and 2146 who did not receive statins. The incidence of developing AF remained lower in statin group than that in control group (2.4% vs. 4.9%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). After PS matching, Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression analyses showed that there was a protective effect of developing AF in a dose-responsive manner. The protective effect was more obvious in subjects with younger age, female gender, hyperlipidemia, coronary artery disease and peripheral artery disease and in subjects without taking angiotensin converting enzyme inhibitor and angiotensin receptor blocker. Our analyses showed that statin therapy was associated with lower risk of newly diagnosed AF in patients with dialysis.
PloS one, 2014
The objective of this study was to test the effect of removal of a ureteral obstruction (renal ca... more The objective of this study was to test the effect of removal of a ureteral obstruction (renal calculus) from anesthetized patients on the perfusion index (PI), as measured by a pulse oximeter, and on the estimated glomerular filtration rate (eGFR). This prospective study enrolled 113 patients with unilateral ureteral obstructions (kidney stones) who were scheduled for ureteroscopy (URS) laser lithotripsy. One urologist graded patient hydronephrosis before surgery. A pulse oximeter was affixed to each patient's index finger ipsilateral to the intravenous catheter, and a non-invasive blood pressure cuff was placed on the contralateral side. Ipsilateral double J stents and Foley catheters were inserted and left indwelling for 24 h. PI and mean arterial pressure (MAP) were determined at baseline, 5 min after anesthesia, and 10 min after surgery; eGFR was determined at admission, 1 day after surgery, and 14 days after surgery. Patients with different grades of hydronephrosis had sim...
Cardiovascular research, 2015
TNF-alpha (TNF-α) causes left ventricular diastolic dysfunction. Down-regulation of sarcoplasmic ... more TNF-alpha (TNF-α) causes left ventricular diastolic dysfunction. Down-regulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a protein (SERCA2a) expression is one of the major mechanisms underlying diastolic dysfunction. We investigated whether TNF-α modulates SERCA2a expression and alters cardiac diastolic function, and its detailed signalling pathway. We used both in vitro cellular cardiomyocyte model and in vivo rat model to address this issue. We found that TNF-α decreased the levels of both SERCA2a mRNA and protein in the cardiomyocytes, with corresponding impairment of diastolic calcium reuptake, a cellular phenotype of cardiac diastolic function. An ∼2 kb promoter of the SERCA2a gene (atp2a2) along with its serial deletions was cloned into the luciferase reporter system. TNF-α significantly decreased the promoter activity, and truncation of the SERCA2a gene promoter with the putative nuclear factor kappa-B (NF-κB) response element abolished TNF-α-induced SERCA2a gene suppression...
PLoS ONE, 2013
Background: Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal... more Background: Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC.
Acta Cardiologica Sinica, 2017
Drug-eluting stents are widely used in coronary artery intervention. However, vessel caging and v... more Drug-eluting stents are widely used in coronary artery intervention. However, vessel caging and very late thrombotic events are of persistent and substantial concern. Bioresorbable vascular scaffolds (BVS) were developed to deliver vascular reparative therapy, by eliminating permanent mechanical restraint. However, data regarding its clinical performance is lacking. After the BVS implantation procedure received national approval in May 2014, patients receiving BVS implantation until November 2014 in National Taiwan University Hospital (NTUH) were enrolled. Clinical variables, angiographic data, procedural details, and follow-up information were collected and compared with those receiving BVS at NTUH as part of the global ABSORB EXTEND trial. A total of 35 patients (38 target vessels) with 48 BVS implanted after approval were enrolled, as the "real-world practice" group. Data of the 34 patients (34 target vessels) with 37 BVS implanted in the ABSORB EXTEND trial were also o...
Annals of medicine, Jan 7, 2017
Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac... more Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by ISHNE and HRS/EHRA/APHRS were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before. This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria. A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased 71...
Journal of Clinical Lipidology, 2017
Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dial... more Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels &amp;amp;amp;amp;amp;lt;130 mg/dL, high-sensitivity C-reactive protein levels of ≥1.5 mg/L, and LVDD, diagnosed by conventional and tissue Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P &amp;amp;amp;amp;amp;lt; .001). Follow-up TDI showed significant improvement of early mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site (Nominal change for E/Emedial: -5.01 ± 6.36 vs 1.80 ± 6.59 for atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SRIVR, 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671).
Clinical Science, 2017
Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries.... more Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies have shown that risk factors for CAE were related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays. Wilcoxon's rank sum tests revealed 89 genes with significantly different methylation levels (P<0.05 and Δβ > |0.1|). Functional characterization using the DAVID database and gene set enrichment analysis indicated that these genes were involved in immune and inflammatory responses. Of these genes 6 were validated in 29 CAE patients and 87 matched individuals with CAE, using pyro-sequencing. TLR6 and NOTCH4 showed significant differences in methylation between the two groups, and lower protein levels of toll-like receptor 6 (TLR6) were detected in CAE patients. In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE.
Acta Cardiologica Sinica, 2013
The objective of this study was to evaluate the renin-angiotensin system genetic effects and phar... more The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients. Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models. Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE in...
Medicine, 2016
Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane pro... more Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505-5.545, P = 0.001; and OR 2.55, 95% CI = 1.428-4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025-3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.
Zhonghua Minguo xin zang xue hui za zhi = Acta Cardiologica Sinica, 2016
The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump... more The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping(TM) (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation o...
Scientific Reports, 2016
Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failu... more Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short-axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age (1.87, 95% CI: 0.61-3.13, p = 0.004) and ECV (3.77, 95% CI: 2.72-4.81, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) were positively associated with Tmv. The results remained robust in certain subgroups. In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is closely related to LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s underlying mechanisms leading to poor prognosis.
Nature communications, Jan 2, 2016
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide as... more Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10(-24)). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor...
PloS one, 2016
Patients with severe kidney function impairment often have autonomic dysfunction, which could be ... more Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. A total of 132 ...
Scientific reports, Jan 19, 2015
Heart failure with preserved ejection fraction (HFPEF) is characterized by myocardial interstitia... more Heart failure with preserved ejection fraction (HFPEF) is characterized by myocardial interstitial fibrosis. A total of 146 patients with HFPEF, were recruited. HFPEF severity was determined using Doppler imaging (E/Em) and also cardiac magnetic resonance imaging (CMRI). Canine modeling of HFPEF was induced by aortic banding. Hemodynamic and echocardiographic data were obtained before and after pressure loading and myocardial Galectin-3 was determined. Mechanical stretch of cultured cardiomyocytes served as the cellular model of HFPEF. Patients with severe HFPEF had significantly higher plasma Galectin-3 levels. Significant correlation between plasma Galectin-3 and E/Em in advanced HFPEF patients was noted. After 2 weeks of pressure overload in canine models, the protein expression of Galectin-3 from LV myocardial tissue was significantly increased (p < 0.01) compared with controls. Galectin-3 expression paralleled the severity of LV diastolic dysfunction by evaluation of CMRI (r...
The Journal of clinical endocrinology and metabolism, Jan 24, 2015
The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to... more The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum ATPase (SERCA). Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and 3 patients with idiopathic hyperaldosteronism), and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation (F/NMD) were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells (HAOSMCs) Setting: Academic clinical research center Participants: Thirty-five patients with PA...
International Journal of Cardiology, 2015
Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation ... more Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation (AF) in dialysis patients is unclear. We used a database from the Registry for Catastrophic Illness from the National Health Research Institute. All dialysis patients aged 18 or older without history of AF before ESRD were incorporated. A total of 113,191 dialysis patients were enrolled in the study. The median follow-up time was 4.17years. We collected information on prescribed drug dosage, number of days of treatment and the total number of pills dispensed from the outpatient pharmacy prescription database. All individuals in the study cohort with the first occurrence of AF were included as cases. In spironolactone group, the incidence of developing new AF was significantly lower than that in the control group both before (0.8% vs. 3.3%, P=0.019) and after PS matching (1.2% vs. 3.0%, P=0.019). Before PS matching, Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression analyses showed that spironolactone was associated with 60% reduction of new AF (HR=0.372 [0.200-0.692], P=0.002) and the protective effect is dose-responsive in accumulated dose, treatment duration and mean daily dose. After PS matching, the overall AF prevention effect remained significant (HR=0.400 [0.179-0.895], P=0.026) while the dose-response relationship became borderline significant. Subgroup analyses showed that the protective effect was more evident in some specific subgroup patients. Our study showed that spironolactone therapy was associated with lower risk of developing AF in a dose-responsive manner in patients with dialysis. Further randomized study is needed to confirm this observation.
Atherosclerosis, 2015
Pericardial fat (PF) has been hypothesized to exert local pathogenic effects on nearby cardiac st... more Pericardial fat (PF) has been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity which might be associated with the presence of arrhythmia or even worse outcomes. The aims of this study was to characterize the relationship between PF and the prognosis in patients with systolic heart failure (HF). This is a retrospective cohort study of a cardiac magnetic resonance imaging (CMRI) database from 2004 to 2011. Fifty patients with systolic HF underwent CMRI examinations were included. We also enrolled twenty patients with HF as the control group. The cine imaging was analyzed to derive total PF volumes, left ventricular volumes and mass and left ventricular ejection fraction by using a previously validated technique. The outcomes, including ventricular tachycardia (VT), ventricular fibrillation (VF) and total mortality were obtained by reviewing medical records. After a median follow-up of 694 days, patients with VT/VF had significant larger indexed PF volumes than those without [36.3 (32.8-43.1) ml/m(2) vs. 24.1 (20.2-27.6) ml/m(2), p = 0.001]. The mortality group also had significant larger indexed PF volumes (PF/body surface area) than those without [31.3 (22.8-38.4) ml/m(2) vs. 23.9 (19.8-27.3) ml/m(2), p = 0.010]. Indexed PF volumes were associated with the development of VT/VF (Hazard ratio, 7.510; 95% C.I, 0.901-62.582, p = 0.062) and mortality (Hazard ratio, 3.998; 95% C.I, 1.077-14.845, p = 0.038) by Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s regression analyses. PF is associated with the development of VT/VF and long-term overall mortality in patients with systolic HF.
Medicine, 2015
Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dial... more Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43-3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45-2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients.
International Journal of Cardiology, 2015
The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in... more The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in dialysis patients. We used a database from the Registry for Catastrophic Illness from the National Health Research Institute (NHRI), which encompasses almost 100% of the patients receiving dialysis started from 1997 to 2008 in Taiwan. All dialysis patients aged 18 or older without history of cardiovascular events in 1997 and 1998 were incorporated. Finally, 113,191 dialysis patients were enrolled. We used propensity score (PS) matching method and Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression models to estimate hazard ratios for AF events for statin users vs. nonusers. In statin group, the incidence of developing new AF was significantly lower than that in control group (1.1% vs. 3.8%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The PS-based selection process identified 2146 patients receiving statins and 2146 who did not receive statins. The incidence of developing AF remained lower in statin group than that in control group (2.4% vs. 4.9%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). After PS matching, Cox&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proportional hazard regression analyses showed that there was a protective effect of developing AF in a dose-responsive manner. The protective effect was more obvious in subjects with younger age, female gender, hyperlipidemia, coronary artery disease and peripheral artery disease and in subjects without taking angiotensin converting enzyme inhibitor and angiotensin receptor blocker. Our analyses showed that statin therapy was associated with lower risk of newly diagnosed AF in patients with dialysis.
PloS one, 2014
The objective of this study was to test the effect of removal of a ureteral obstruction (renal ca... more The objective of this study was to test the effect of removal of a ureteral obstruction (renal calculus) from anesthetized patients on the perfusion index (PI), as measured by a pulse oximeter, and on the estimated glomerular filtration rate (eGFR). This prospective study enrolled 113 patients with unilateral ureteral obstructions (kidney stones) who were scheduled for ureteroscopy (URS) laser lithotripsy. One urologist graded patient hydronephrosis before surgery. A pulse oximeter was affixed to each patient's index finger ipsilateral to the intravenous catheter, and a non-invasive blood pressure cuff was placed on the contralateral side. Ipsilateral double J stents and Foley catheters were inserted and left indwelling for 24 h. PI and mean arterial pressure (MAP) were determined at baseline, 5 min after anesthesia, and 10 min after surgery; eGFR was determined at admission, 1 day after surgery, and 14 days after surgery. Patients with different grades of hydronephrosis had sim...
Cardiovascular research, 2015
TNF-alpha (TNF-α) causes left ventricular diastolic dysfunction. Down-regulation of sarcoplasmic ... more TNF-alpha (TNF-α) causes left ventricular diastolic dysfunction. Down-regulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a protein (SERCA2a) expression is one of the major mechanisms underlying diastolic dysfunction. We investigated whether TNF-α modulates SERCA2a expression and alters cardiac diastolic function, and its detailed signalling pathway. We used both in vitro cellular cardiomyocyte model and in vivo rat model to address this issue. We found that TNF-α decreased the levels of both SERCA2a mRNA and protein in the cardiomyocytes, with corresponding impairment of diastolic calcium reuptake, a cellular phenotype of cardiac diastolic function. An ∼2 kb promoter of the SERCA2a gene (atp2a2) along with its serial deletions was cloned into the luciferase reporter system. TNF-α significantly decreased the promoter activity, and truncation of the SERCA2a gene promoter with the putative nuclear factor kappa-B (NF-κB) response element abolished TNF-α-induced SERCA2a gene suppression...
PLoS ONE, 2013
Background: Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal... more Background: Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC.