Moni Nader - Academia.edu (original) (raw)

Papers by Moni Nader

Acta diabetologica, May 20, 2024

Journal of the American College of Cardiology, Apr 1, 2024

Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors. ... more Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors. This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD. Methods: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data. Results: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results. Conclusions: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup.

Lipids in health and disease, Feb 22, 2024

Background Type 2 Diabetes (T2D) is influenced by genetic, environmental, and ageing factors. Age... more Background Type 2 Diabetes (T2D) is influenced by genetic, environmental, and ageing factors. Ageing pathways exacerbate metabolic diseases. This study aimed to examine both clinical and genetic factors of T2D in older adults. Methods A total of 2,909 genotyped patients were enrolled in this study. Genome Wide Association Study was conducted, comparing T2D patients to non-diabetic older adults aged ≥ 60, ≥ 65, or ≥ 70 years, respectively. Binomial logistic regressions were applied to examine the association between T2D and various risk factors. Stepwise logistic regression was conducted to explore the impact of low HDL (HDL < 40 mg/dl) on the relationship between the genetic variants and T2D. A further validation step using data from the UK Biobank with 53,779 subjects was performed. Results The association of T2D with both low HDL and family history of T2D increased with the age of control groups. T2D susceptibility variants (rs7756992, rs4712523 and rs10946403) were associated with T2D, more significantly with increased age of the control group. These variants had stronger effects on T2D risk when combined with low HDL cholesterol levels, especially in older control groups. Conclusions The findings highlight a critical role of age, genetic predisposition, and HDL levels in T2D risk. The findings suggest that individuals over 70 years who have high HDL levels without the T2D susceptibility alleles may be at the lowest risk of developing T2D. These insights can inform tailored preventive strategies for older adults, enhancing personalized T2D risk assessments and interventions.

The FASEB Journal, Mar 31, 2016

Mounting evidence implicates striatin in regulating cardiac function by virtue of its interaction... more Mounting evidence implicates striatin in regulating cardiac function by virtue of its interaction with regulators of the L-type calcium channel (LCC), i.e. caveolin-3, protein phosphatase 2A, and calmodulin. We have previously shown that knockdown (KD) of striatin using shRNA (shRNA-STRN) in neonatal rat cardiomyocytes reduced the rate of their spontaneous contraction and desensitized them to isoproterenol. We aimed to explore if the expression of STRN is altered during cardiac remodeling using Spontaneously Hypertensive Rats (SHR) and if STRN modulates the adrenergic response in cardiomyocytes. Herein, we show that STRN expression is higher in the left ventricle (LV) of SHR when compared to Wistar Kyoto (WKY) rats at the age of 4 weeks. Surprisingly, at the age of 18 weeks, the expression of STRN in LV was less in SHR when compared to WKY rats. KD of STRN in cultured cardiomyocytes did not affect the expression of the LCC. However, confocal microscopy revealed that an isoproterenol challenge resulted in ...

Reviews in Endocrine and Metabolic Disorders, Dec 7, 2023

Frontiers in Physiology, Jul 11, 2023

Editorial on the Research Topic Trends post-COVID-19 attack: the cardiocerebral system safety rem... more Editorial on the Research Topic Trends post-COVID-19 attack: the cardiocerebral system safety remains of utmost concern Survivors of COVID-19 infected individuals continue to suffer from a myriad of longterm sequelae that affect most organ systems of the body. To a higher degree, the preponderance of cardiovascular and cerebral sequalae of COVID-19 infection requires an in-depth analysis of these occurrences to decelerate or halt its expansion. Whereas cardiovascular manifestation of acute COVID-19 infection, including myocardial infarction, pericarditis, vascular thromboembolism, and cardiac arrhythmias, have been well described, (Abdel Moneim et al., 2022), longer-term consequences following recovery from symptomatic or asymptomatic infection remain incompletely understood. Given the large number of patients who survived COVID-19 infection worldwide, describing aberrations in cardiovascular and nervous system physiology may provide insight into mechanisms and potentially therapies for this illness. This Research Topic of the Journal includes original studies and reviews that provide novel insight into the genesis of cardiac and neurological consequences of COVID-19. Such data may illuminate the development of novel therapeutic interventions to these patients. In a review, Batta et al., addressed the cardiovascular symptoms in COVID-19 patients with a focus on vascular dysfunction, arrhythmias, myocardial ischemia, and discussed the most updated recommendations for the treatment of COVID-19. We previously reported the presence of almost all the receptors of SARS-CoV-2 on cardiomyocytes which makes the heart a favorable target for this virus (Abdi et al., 2022). Batta et al. indicated that the vascular endothelial dysfunction is involved in the pathogenesis of SARS-CoV-2 and hence the activation of pro-inflammatory cytokines leading to increased vascular permeability and thrombosis in many organs. Tachycardia was the most common cardiac presentation associated with SARS-CoV-2 infection, along with arrhythmias and conduction blocks, myocardial ischemia and injury, and hypertension. Interestingly, the authors reported that the elevated ACE-2 expression on endothelial cells of COVID-19 patients' lungs indicates an elevated pro-hypertensive angiotensin II level leading to vasoconstriction and aldosterone

Research Square (Research Square), Apr 14, 2022

Background: The COVID-19 pandemic claimed millions of lives worldwide without clear signs of abat... more Background: The COVID-19 pandemic claimed millions of lives worldwide without clear signs of abating. There have been tremendous interests in understanding the etiology of the disease particularly in what makes it fatal in certain patients. Methods: This study investigated 819 COVID-19 patients admitted to the COVID-19 ward at a tertiary care center in Lebanon and evaluated their vital signs and biomarkers while probing for two main outcomes: intubation and fatality. Results: Correlation analysis of various comorbidities revealed that hypertension, diabetes, being overweight, kidney disease, cardiovascular disease, autoimmune disease, and gender are independent risk factors for both intubation and fatality. Shortness of breath, age and being overweight correlated with intubation while fatality correlated with shortness of breath in our group of patients. Elevated level of serum creatinine was the highest correlating factor with fatality, while both white blood count and serum glutamic-oxaloacetic transaminase levels emerged as independent risk factors for intubation. Conclusions: Collectively our data show that high creatinine levels are signi cantly associated with fatality in our COVID-19 study patients, underscoring the importance of kidney function as a main modulator of SARS-CoV-2 morbidity and favor a careful management of patients with elevated creatinine levels on admission. storm yielding an abundance of proin ammatory cytokines such as interleukin-1, interleukin-4, interleukin-6 and interleukin-10 (3). This cytokine storm, combined with chronic conditions such as cancer, diabetes, lung or kidney diseases and cardiac conditions, underscored critical and fatal COVID-19 outcomes. Other factors including obesity and gender have been shown to correlate with the severity of COVID-19 symptoms. The sickest COVID-19 patients, or those who were admitted to the intensive care unit (ICU) were often obese subjects irrespective of their age (4). While some comorbid factors for COVID-19 are established in certain populations, others have been shown to be population-speci c (5, 6). For example, the fatality ratio in the majority of populations is about 3.5 male to female (7-9), except in India where COVID-19 fatality rate was shown to be higher in women than men (3.3% vs 2.9%) (10, 11). The SARS-CoV-2 infection is not limited to the upper respiratory tract and lungs, but commonly affects multiple organs including the heart, liver, and kidneys (12-14). Moreover, multiorgan failure has been associated with many COVID-19 cases worldwide. Hospitalized COVID-19 patients often presented upon admission with acute respiratory distress syndrome, disseminated intravascular coagulation disease, venous thromboembolism, bone marrow failure, acute kidney injury, myocarditis, neurological manifestations, among others (15). Overall, a signi cant number of COVID-19 patients developed acute kidney injury (AKI) secondary to COVID-19. These variabilities in the clinical manifestations of COVID-19 call for a necessity to investigate various risk factors associated with fatality in COVID-19 patients and in different populations to account for inter-patient, clinical, and demographic variabilities. According to the Ministry of Public Health in Lebanon, there were more than 1 million con rmed cases and more than 9,800 deaths at the time of this writing. Although 20% of the population was infected, and close to 2% of the con rmed infections were fatal, there is no systemic study that explored the risk factors associated with COVID-19 in Lebanon. Herein, we evaluated the clinical manifestations in a group of 819 COVID-19 patients with critical/fatal and non-critical illness from one of the largest tertiary care centers in Lebanon. We investigated and identi ed several risk factors for their association with severe COVID-19 and/or fatality. These factors can be used to build a comprehensive clinical platform for a better management of COVID-19 patients. Materials And Methods Patients We investigated 819 COVID-19 patients who were admitted between January 2020 and April 2021 to the COVID-19 ward at a major tertiary care hospital in Lebanon. Patients were evaluated upon admission and were admitted to the COVID-19 ward if they tested positive for the SARS-CoV-2 by quantitative realtime reverse transcriptase-polymerase chain reaction (qRT-PCR) of nasopharyngeal swabs using LightMix Modular SARS-CoV-2 E, N, and RdRP-genes (TibMolbiol, Berlin, Germany) performed according to manufacturer's manual. COVID-19 diagnosis was made according to the World Health Organization guidance (https://www.who.int/publications/i/item/diagnostic-testing-for-sars-cov-2). Anonymized electronic medical records of all patients were retrieved and reviewed for epidemiological, demographic, clinical and laboratory data. Clinical data on admission included clinical symptoms, biochemical markers on admission, previous medical conditions, oxygen requirement, the need for and the duration of intubation, and the length of hospital stay. Statistical analysis admission to avoid deadly complications. Finally, special attention must be given to hypertensive subjects with reduced kidney function to reduce their mortality rate from SARS-CoV-2 infection.

Journal of Public Health, Apr 5, 2023

Background Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety ... more Background Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon. Methods Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed. Results Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35-55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P = 0.036). Conclusions Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees.

Dans notre étude nous avons caractérisé la localisation et la distribution, pour la première fois... more Dans notre étude nous avons caractérisé la localisation et la distribution, pour la première fois, de l'ET-1 et de ces deux types de récepteurs ET A et ET B dans les noyaux isolés des cellules hépatiques et du MLV humaines, de lapin et du rat. Nous avons aussi démontré que la densité de l'ET-1 et de ces deux types de récepteurs au niveau nucléaire dépend du type cellulaire et de l'espèce animale utilisés. Nous avons aussi démontré que l'ET-1 extranucléaire induit une augmentation soutenue du [Ca]n dans les noyaux isolés des hépatocytes humains, de lapin et du rat avec une cinétique d'augmentation du [Ca]n différente d'une espèce animale à l'autre. Nous avons aussi démontré que l'effet induit par l'ET-1 sur l'augmentation du calcium libre nucléaire est surtout dû au récepteur ET B et que le récepteur ET A joue plutôt un rôle dans le freinage (antagoniste physiologique) de l'augmentation du [Ca] n massive induite par l'ET-l. Dans une deuxième partie de notre étude, nous avons identifié, pour la première fois, la présence de l'Ang II et de ces deux types de récepteurs dans les noyaux isolés des CMLV et des hépatocytes humains, de lapin et du rat. Notre étude a aussi montré que la densité nucléaire de l'Ang Il et de ces deux types de récepteur AT 1 et AT 2 dépend du type cellulaire et de l'espèce animale utilisée. Nous avons aussi démontré que l'Ang II extranucléaire induit une augmentation transitoire du [Ca]n dans les noyaux isolés des hépatocytes humains, de lapin et du rat avec une cinétique dépendante de l'espèce animale. Nous avons démontré que l'augmentation du [Ca]n induite par l'Ang II est surtout due à l'activation du récepteur nucléaire AT 1 et que le récepteur AT 2 joue plutôt un rôle dans le soutien de l'effet de l'Ang II. La troisième partie de notre étude porte sur la présence et la fonction du NHE-1 au niveau nucléaire. Nous avons démontré pour la première fois la présence du NHE-1 au niveau des noyaux isolés des hépatocytes et des CMLV humaines, de lapin et du rat notamment au niveau des membranes de l'enveloppe nucléaire. Notre étude suggère que la densité du NHE-1 nucléaire dépend du type cellulaire et de l'espèce animale utilisée. Notre étude suggère aussi que le NHE-1 des membranes nucléaires est fonctionnel et que son activation dépend en même temps d'une surcharge sodique cytosolique et d'un pH acide nucléaire. Nous avons aussi caractérisé la direction du NHE-1 nucléaire qui semble être dans le même sens que celui de la membrane de surface. Ce NHE-1 des membranes de l'enveloppe nucléaire contribue à la modulation du niveau du [Na]n. Donc en conclusion cette étude suggère que la présence, la densité et la distribution nucléaires de l'ET-1 et de ses deux types de récepteurs ET A et ET B, de l'Ang II et de ces deux types de récepteurs AT 1 et AT 2 , ainsi que du NHE-1 dépendent du type cellulaire et de l'espèce animale utilisée. De plus, l'augmentation soutenue du [Ca]n, induite par l'ET-1 est surtout due à l'activation du récepteur ETB nucléaire et celle transitoire induite par l'Ang II est principalement due à l'activation du récepteur AT 1 nucléaire. Cette étude suggère aussi que le NHE-1 des membranes nucléaires est fonctionnel à ce niveau et module le niveau du [Na]n

Journal of Biological Chemistry, Oct 1, 2003

Lysophosphatidic acid (LPA) is a bioactive molecule involved in inflammation, immunity, wound hea... more Lysophosphatidic acid (LPA) is a bioactive molecule involved in inflammation, immunity, wound healing, and neoplasia. Its pleiotropic actions arise presumably by interaction with their cell surface G protein-coupled receptors. Herein, the presence of the specific nuclear lysophosphatidic acid receptor-1 (LPA 1 R) was revealed in unstimulated porcine cerebral microvascular endothelial cells (pCMVECs), LPA 1 R stably transfected HTC4 rat hepatoma cells, and rat liver tissue using complementary approaches, including radioligand binding experiments, electron-and cryomicroscopy, cell fractionation, and immunoblotting with three distinct antibodies. Coimmunoprecipitation studies in enriched plasmalemmal fractions of unstimulated pCMVEC showed that LPA 1 Rs are dually sequestrated in caveolin-1 and clathrin subcompartments, whereas in nuclear fractions LPA 1 R appeared primarily in caveolae. Immunofluorescent assays using a cell-free isolated nuclear system confirmed LPA 1 R and caveolin-1 co-localization. In pCMVEC, LPA-stimulated increases in cyclooxygenase-2 and inducible nitricoxide synthase RNA and protein expression were insensitive to caveolea-disrupting agents but sensitive to LPAgenerating phospholipase A 2 enzyme and tyrosine kinase inhibitors. Moreover, LPA-induced increases in Ca 2؉ transients and/or iNOS expression in highly purified rat liver nuclei were prevented by pertussis toxin, phosphoinositide 3-kinase/Akt inhibitor wortmannin and Ca 2؉ chelator and channel blockers EGTA and SK&F96365, respectively. This study describes for the first time the nucleus as a potential organelle for LPA intracrine signaling in the regulation of pro-inflammatory gene expression.

The FASEB Journal, Apr 1, 2015

Vascular Health and Risk Management, 2023

The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported ... more The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis. Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries. Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD. Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.

Canadian Journal of Physiology and Pharmacology, Aug 1, 2008

Our previous work showed that ET-1 induced a concentration-dependent increase of cytosolic Ca2+ (... more Our previous work showed that ET-1 induced a concentration-dependent increase of cytosolic Ca2+ ([Ca]c) and nuclear Ca2+ ([Ca]n) in human aortic vascular smooth muscle cells (hVSMCs). In the present study, using hVSMCs and 3-dimensional confocal microscopy coupled to the Ca2+ fluorescent probe Fluo-3, we showed that peptidic antagonists of ETA and ETB receptors (BQ-123 (10−6 mol/L) and BQ-788 (10−7 mol/L), respectively) prevented, but did not reverse, ET-1-induced sustained increase of [Ca]c and [Ca]n. In contrast, nonpeptidic antagonists of ETA and ETB (respectively, BMS-182874 (10−8–10−6 mol/L) and A-192621 (10−7 mol/L)) both prevented and reversed ET-1-induced sustained increase of [Ca]c and [Ca]n. Furthermore, activation of the ETB receptor alone using the specific agonist IRL-1620 (10−9 mol/L) induced sustained increases of [Ca]c and [Ca]n, and subsequent administration of ET-1 (10−7 mol/L) further increased nuclear Ca2+. ET-1-induced increase of [Ca]c and [Ca]n was completely blocked by extracellular application of the Ca2+ chelator EGTA. Pretreatment with the G protein inhibitors pertussis toxin (PTX) and cholera toxin (CTX) also prevented the ET-1 response; however, strong membrane depolarization with KCl (30 mmol/L) subsequently induced sustained increase of [Ca]c and [Ca]n. Pretreatment of hVSMCs with either the PKC activator phorbol-12,13-dibutyrate or the PKC inhibitor bisindolylmaleimide did not affect ET-1-induced sustained increase of intracellular Ca2+. These results suggest that both ETA- and ETB-receptor activation contribute to ET-1-induced sustained increase of [Ca]c and [Ca]n in hVSMCs. Moreover, in contrast to the peptidic antagonists of ET-1 receptors, the nonpeptidic ETA-receptor antagonist BMS-182874 and the nonpeptidic ETB-receptor antagonist A-192621 were able to reverse the effect of ET-1. Nonpeptidic ETA- and ETB-receptor antagonists may therefore be better pharmacological tools for blocking ET-1-induced sustained increase of intracellular Ca2+ in hVSMCs. Our results also suggest that the ET-1-induced sustained increase of [Ca]c and [Ca]n is not mediated via activation of PKC, but via a PTX- and CTX-sensitive G protein calcium influx through the R-type Ca2+ channel.

Current angiogenesis, 2014

Heliyon

Background and objectives: High homocysteine levels are associated with increased risk of hyperte... more Background and objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes. Methods and results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically

European Heart Journal

Conclusion: 24h DEX pre-treatment significantly increased left-ventricular contractile force in L... more Conclusion: 24h DEX pre-treatment significantly increased left-ventricular contractile force in Langendorff-perfused hearts. Interestingly, DEX-pretreatment stimulated SOCE, which may explain the DEX-dependent increase in Ca transient amplitude. This is supported by data showing that inhibition of SOCE by SKF could abolish the increase in Ca transient-amplitude and fractional shortening. Thus, activation of SOCE may functionally link GC-receptor stimulation to enhanced calcium cycling and positive inotropy.

International Journal of Child Health and Nutrition, 2020

Context: Several decades of dietary research recommended the consumption of antioxidants and vita... more Context: Several decades of dietary research recommended the consumption of antioxidants and vitamins rich foods as a protective tool against a broad portfolio of diseases Aims: This study aims to test if oral supplementation of natural antioxidants and vitamins before the winter season, may reduce the occurrence of upper respiratory tract infection (URTI) in adolescents. Settings and Design: Natural antioxidants and vitamins supplements were given to 90 adolescents (45 males, and 45 females) from an orphanage against a placebo during three months in a double-blind fashion. Methods and Material: Saliva was collected before and after supplementation. The antioxidant activity of saliva was determined in vitro using electrolysis as a free radical generating system. Additionally, total antioxidant activity, glutathione and ascorbic acid levels in the saliva were evaluated before and after supplementation. The URTI frequency was recorded throughout the winter season (3 months). Statistical Analysis: All values were expressed as means ± SEM. Significance of the results was assessed using Student's t-test and Fisher's test Results: Data indicated that only five individuals from the group that received antioxidants and vitamins supplements manifested URTI while 14 adolescents from the non-supplemented group showed symptoms of URTI. Biochemical analysis revealed that the saliva in provenance from the supplemented group exhibited a higher capacity to scavenge free radicals compared to its capacity before supplementation. This supplementation also increased the total antioxidant activity and the levels of both ascorbic acid and glutathione in the saliva. Conclusions: We concluded that oral intake of antioxidants and vitamins protects against URTI through increased antioxidant activity.

Canadian Journal of Physiology and Pharmacology, Aug 1, 2010

Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-... more Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-1, ET A , and ET B receptors in isolated human aortic vascular endothelial cells (hVECs). The level of the peptide and its receptors was significantly higher in the nucleus (including the nuclear envelope membranes) than in the cytosol (including the cell membrane). Furthermore, using the Western blot technique we demonstrated the presence of both ETA and ETB receptors. Using intact and isolated human hVECs and the Fura-2 calcium (Ca 2+) measurement technique, we showed that ET-1 induced a dose-dependent increase of total intracellular free Ca 2+ , with an EC50 of 1.3 Â 10-10 mol/L. The specific ETA receptor antagonist ABT-627 (10-7 mol/L), but not the ETB receptor antagonist A-192621 (10-7 mol/L), prevented the ET-1 (10-9 mol/L) induced increase of total intracellular Ca 2+. In conclusion, these results clearly show that similar to ETB receptors, ETA receptors are also present in human aortic vascular endothelial cells and their levels are higher than ETB in the nucleus when compared with the cytosol. Furthermore, we suggest that ETA, but not ETB, receptors mediate the effect of ET-1 on total intracellular Ca 2+ of human aortic vascular endothelial cells.

Vascular Health and Risk Management

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Reva... more Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

PLOS ONE

Background The COVID-19 pandemic claimed millions of lives worldwide without clear signs of abati... more Background The COVID-19 pandemic claimed millions of lives worldwide without clear signs of abating despite several mitigation efforts and vaccination campaigns. There have been tremendous interests in understanding the etiology of the disease particularly in what makes it severe and fatal in certain patients. Studies have shown that COVID-19 patients with kidney injury on admission were more likely to develop severe disease, and acute kidney disease was associated with high mortality in COVID-19 hospitalized patients. Methods This study investigated 819 COVID-19 patients admitted between January 2020-April 2021 to the COVID-19 ward at a tertiary care center in Lebanon and evaluated their vital signs and biomarkers while probing for two main outcomes: intubation and fatality. Logistic and Cox regressions were performed to investigate the association between clinical and metabolic variables and disease outcomes, mainly intubation and mortality. Times were defined in terms of admissio...