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Papers by ALKISTIS KAPELOUZOU

Stem Cell Biology and Regenerative Medicine, 2019

The presence of a continuously renewing squamous cell epithelium that covers the esophagus demons... more The presence of a continuously renewing squamous cell epithelium that covers the esophagus demonstrates the crucial role of a pluripotent stem cell population that regulates esophageal homeostasis and pathogenesis of the most esophageal diseases. Esophageal development and maintenance of adult esophageal homeostasis share common mechanisms, as transformation of early columnar esophageal epithelium into mature squamous epithelial cells is based on molecular regulators such as SOX2, p63, Notch, and NANOG, which are also present in fetal esophageal development. In addition, esophageal cancer seems to be associated with the cancer stem cell hypothesis, which refers to mutated pluripotent stem cell populations that give rise to cancerous cell accumulations. These mutations have been related to stem cell markers like aldehyde dehydrogenase-1 (ALDH1), Lgr5, Wnt/β-catenin, Notch, CD44, and CD177. Dietary habits, like alcohol consumption, and caustic injury of the esophagus have been correlated to such mutations and consequent carcinogenesis. Moreover, Barrett’s esophagus due to gastroesophageal reflux disease (GERD), which is a precancerous lesion that leads to esophageal adenocarcinoma, rises from either a native squamous esophageal stem cell population that turns into intestinal epithelial cell (transdifferentiation) or an intestinal esophageal stem cell population derived from the esophagus, stomach, or circulation (transcommitment), which turns immortal due to mutations in the stem cell markers Sox9, Sox2, p63, Cdx1, Cdx2, and Foxa2. Nevertheless, esophageal cancer stem cell-regulating molecules could be ideal pharmaceutic targets for future therapeutic attempts against esophageal cancer. Furthermore, stem cell technology could enhance tissue-engineering esophageal scaffolds in order to replace damaged esophageal segments with transplanted artificial segments, after radical surgical operations due to esophageal cancer, massive esophageal caustic injury, endoscopic esophageal dissection due to Barrett’s esophagus, ionizing radiation, and pediatric diseases, such as esophageal atresia or tracheoesophageal fistula.

Annals of Esophagus, 2021

Background Esophageal cancer (EC) is considered the sixth most common cause of cancer related mor... more Background Esophageal cancer (EC) is considered the sixth most common cause of cancer related mortality worldwide based on recent medical literature data, accounting for 400,200 deaths in Western countries (1,2). Neoadjuvant chemotherapy with or without radiotherapy and surgical resection along with lymph node (LN) dissection is considered the mainstay of treatment for EC. Despite the fact that there have been significant improvements in multimodality therapies, operative and perioperative management, the overall 5-year survival rate remains moderate; reaching 25-50%, meaning that almost a half of EC patients will develop recurrence after esophagectomy mostly within months or few years (3). The group of patients with a recurrence are candidates for systemic chemotherapy but median survival is still poor (6.0-8.2 months) (4). The most common sites of recurrence are distant LNs, liver, brain, lung, and bone. The types and locations of recurrence considerably differ among individual patients mainly categorized as locoregional at the site of

Hellenic Journal of Cardiology, 2021

BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce card... more BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and; surgical procedures. However, it is unclear whether RIPC has protective effects in patients; undergoing the transfemoral transcatheter aortic valve implantation (TF-TAVΙ) procedure. METHODS Between September 2013 and September 2015, 55 consecutive patients were prospectively randomly assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5 min intermittent leg ischemia and 5 min reperfusion, 33 patients) prior TF-TAVI. The primary endpoint was to determine the serum levels of: hs-cTn-I (necrosis), CK-18 (apoptosis) and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included: total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI) and stroke. RESULTS 22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant differences in serum levels of hs-cTn-I and CK-18 among groups. However, in the RIPC group the IL1b level increase was significantly lower 24h post TF-TAVΙ, (p<0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of 1 month. No RIPC-related adverse events were observed. CONCLUSIONS Our data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in RIPC group.

Cirugía Española, 2021

Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite a... more Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer.

Basic Research in Cardiology, 2021

Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathw... more Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. Methods & Results: We block-randomised 270 patients within 48h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; b) the carotid-femoral pulse wave velocity (PWV); c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 minutes after RIC onset (T3); and d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p<0.05) at T3 following single-than double-cycle inflation (PBR:ΔT0-T3=0.249±0.033 vs 0.126±0.034 μm, p=0.03 and PWV:0.4±0.21 vs-1.02±0.24 m/s, p=0.03). Increased miR-150,-21,-208 (p<0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related with PWV reduction (r=0.763, p<0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) >15% (odds-ratio of 3.75,p=0.029). miR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r=0.40 and 0.37, p<0.05), in the single cycle RIC. Conclusion: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Cytokine, 2019

Background: Adenoid cystic cancer arising in the salivary glands has distinctive features such as... more Background: Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated. Methods: The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed. Results: Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate. Conclusions: The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.

Clinical and Applied Thrombosis/Hemostasis, 2020

Inflammation and coagulation pathways are implicated in circulatory disease, but their interactio... more Inflammation and coagulation pathways are implicated in circulatory disease, but their interaction has not been completely deciphered yet. In this study, we investigated the association of coagulation and inflammation indices (activated clotting time [ACT], C-reactive protein, neutrophils) in hospitalized patients. Blood samples were drawn from consecutive patients at admission and at 48 hours for the assessment of the aforementioned parameters (n = 63). Healthy controls matched for sex and age were also examined (n = 39). Activated clotting time positively correlated with CRP on admission ( r = 0.354, P = .005), while the correlation was more robust on the second day ( r = 0.775, P < .001). Activated clotting time was significantly more prolonged in patients with abnormal CRP or abnormal absolute neutrophil count compared to patients with normal inflammatory markers ( U = 55.0, P < .001 and U = 310.5, P = .035, respectively). At 48 hours, a positive relationship was observed ...

Nutrition and Cancer, 2020

Oncologic patients often suffer from malnutrition which in turn, might have negative impact on tr... more Oncologic patients often suffer from malnutrition which in turn, might have negative impact on treatment outcomes. The Geriatric Nutritional Risk Index (GNRI), as an index of impaired nutritional status, has emerged as a significant prognostic factor for short-and long-term outcomes in cancer patients. The aim of the current systematic review is to determine whether the GNRI is an independent prognostic factor of postoperative complications and survival in cancer patients. A systematic search was conducted to identify studies, published from 2005 to 2019, which assessed associations between GNRI and short-and long-term outcomes in cancer patients. Eighteen studies fulfilled the eligibility criteria and were included in the analysis. Low scores of GNRI were associated with increased risk for developing postoperative complications and impaired survival of cancer patients in most studies. Our findings support the use of the GNRI in the clinical practice, since it is a simple and reliable tool for assessing nutritional status in oncologic patients. More prospective, multi-centered studies are warranted to confirm the current results, as well as the role of nutritional support in improving the prognosis of cancer patients.

Annals of Vascular Surgery, 2020

Purpose: Despite increases in formal education, changing trends affecting epidemiologic practice ... more Purpose: Despite increases in formal education, changing trends affecting epidemiologic practice prompted concerns over whether epidemiologists had sufficient training. Methods: This study sought to explain factors that predicted low self-reported proficiency levels among daily important work tasks of state health agencies' epidemiologists. The number of knowledge gaps, instances where epidemiologists identified a work-related task both as 'very' important in their daily work and felt they were "unable to perform" or performed at a "beginner" level, was studied, and predictor variables were assessed. A total of 681 epidemiologists responded to the 2014 Public Health Workforce Interests and Needs Survey, a national survey of state health agency workers; epidemiologists represented 7% of all respondents. Results: Epidemiologists at state health agencies worked mostly in communicable disease (31%) or general surveillance (26%). Epidemiologists reported eight key daily work-related activities with an average of three training gaps. Factors that decreased the likelihood of epidemiologists' low proficiency in performing key activities were the presence of internal trainings (adjusted odds ratio ¼ 0.69, 95% confidence interval, 0.49e0.99) and length of time working in public health (adjusted odds ratio ¼ 0.95, 95% confidence interval, 0.93e0.98). Conclusion: Although formal education of epidemiologists is on the rise, state health agencies' epidemiologists feel unprepared to tackle one-third of their important daily tasks.

Pediatric Cardiology, 2020

Device closure is the first-line treatment for most atrial septal defects (ASDs). Minimally invas... more Device closure is the first-line treatment for most atrial septal defects (ASDs). Minimally invasive cardiac surgery (MICS) has been found safe and effective for ASD closure with comparable mortality/morbidity and superior cosmetic results compared to conventional median sternotomy. Our goal was to compare percutaneous versus MICS of ASDs. A systematic review was performed using PubMed and the Cochrane Library (end-of-search date on May 22, 2019). Meta-analyses were conducted using fixed and random effects models. In the present systematic review, we analyzed six studies including 1577 patients with ASDs who underwent either MICS (n = 642) or device closure (n = 935). Treatment efficacy was significantly higher in the MICS (99.8%; 95% CI 98.9-99.9) compared to the device closure group (97.3%; 95% CI 95.6-98.2), (OR 0.1; 95% CI 0.02-0.6). Surgical patients experienced significantly more complications (16.2%; 95% CI 13.0-19.9) compared to those that were treated with a percutaneous approach (7.1%; 95% CI 5.0-9.8), (OR 2.0; 95% CI 1.2-3.2). Surgery was associated with significantly longer length of hospital stay (5.6 ± 1.7 days) compared to device closure (1.3 ± 1.4 days), (OR 4.8; 95% CI 1.1-20.5). Residual shunts were more common with the transcatheter (3.9%; 95% CI 2.7-5.5) compared to the surgical approach (0.95%; 95% CI 0.3-2.4), (OR 0.1; 95% CI 0.06-0.5). There was no difference between the two techniques in terms of major bleeding, hematoma formation, transfusion requirements, cardiac tamponade, new-onset atrial fibrillation, permanent pacemaker placement, and reoperation rates. MICS for ASD is a safe procedure and compares favorably to transcatheter closure. Despite longer hospitalization requirements, the MICS approach is feasible irrespective of ASD anatomy and may lead to a more effective and durable repair.

Acta Pharmacologica Sinica, 2020

Circulating or tissue-related biomarkers are of clinical value for risk stratification in patient... more Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects.

Journal of investigative surgery : the official journal of the Academy of Surgical Research, Jan 30, 2018

To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. F... more To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. For this study seventy-two C57BL/6J mice were utilized. Sepsis was induced by cecal ligation and puncture (CLP) in the mice of the three septic (S) groups (euthanized at 24 hours, 48 hours and 72 hours). Sham (laparotomy)- operated mice constituted the control (C) groups (euthanized at 24, 48 and 72 hours). Blood samples were drawn and liver tissues were extracted and examined histologically. The expression of TLRs 2, 3, 4 and 7 was assessed via immunohistochemistry (IHC) and qrt-PCR (quantitative- Polymerase Chain Reaction). Liver function tests were elevated in all S-groups in contrast to their time-equivalent control groups (S24 versus C24, S48 versus C48 and S72 versus C72) (p < 0.05). Liver histology displayed progressive deterioration in the septic groups. IHC and qrt-PCR both showed an increased expression of all TLRs in the septic mice in comparison to their analogous control o...

Therapeutic Advances in Cardiovascular Disease, 2017

Backround: Left atrial (LA) enlargement plays an important role in the development of heart failu... more Backround: Left atrial (LA) enlargement plays an important role in the development of heart failure (HF) and is a robust prognostic factor. Fibrotic processes have also been advocated to evoke HF through finite signalling proteins. Methods: We examined the association of two such proteins, cystatin C (CysC) and galectin-3 (Gal-3), and other clinical, echocardiographic and biochemical parameters with LA volume index (LAVi) in patients with HF with severely impaired left ventricular ejection fraction (LVEF). Severe renal, liver, autoimmune disease and cancer were exclusion criteria. Results: A total of 40 patients with HF (31 men, age 66.6 ± 1.7) with LVEF = 25.4 ± 0.9% were divided into two groups according to the mean LAVi (51.03 ± 2.9 ml/m 2) calculated by twodimensional transthoracic echocardiography. Greater LAVi was positively associated with LV end-diastolic volume (p = 0.017), LV end-systolic volume (p = 0.025), mitral regurgitant volume (MRV) (p = 0.001), right ventricular systolic pressure (RVSP) (p < 0.001), restrictive diastolic filling pattern (p = 0.003) and atrial fibrillation (p = 0.005). Plasma CysC was positively correlated with LAVi (R 2 = 0.135, p = 0.019) and log-transformed plasma Gal-3 (R 2 = 0.109, p = 0.042) by simple linear regression analysis. Stepwise multiple linear regression analysis showed that only MRV (t = 2.236, p = 0.032), CysC (t = 2.467, p = 0.019) and RVSP (t = 2.155, p = 0.038) were significant predictors of LAVi. Conclusions: Apart from known determinants of LAVi, circulating CysC and Gal-3 were associated with greater LA dilatation in patients with HF with reduced LVEF. Interestingly, the correlation between these two fibrotic proteins was positive.

Global Cardiology Science and Practice, 2015

Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals ov... more Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. Methods: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor b1 (TGF-b1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. Results: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1 was negatively correlated with TIMP1. Conclusion: We found that many BMs expressing calcification, collagen breakdown, or formation, and inflammation are increased in the valve tissue and in the serum of patients with CAVS as compared with healthy group. Our findings may give new insights towards diagnosis but also therapy. Thus antisclerostin, and antiflammatory agents could be tried for preventing aortic calcification progression.

Atherosclerosis Supplements, 2010

Journal of cardiovascular medicine (Hagerstown, Md.), 2015

The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obs... more The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obscure. The present study analyzed the serum levels of omentin-1 and chemerin in patients with acute myocardial infarction (AMI) as well as prospectively 6 months post-AMI. Seventy-eight patients (63 men and 15 women) with first AMI were enrolled. Thirty-two age-matched and sex-matched individuals without overt cardiovascular disease served as healthy controls. Serum levels of omentin-1, chemerin, interleukin-18 (IL-18), high-sensitivity C-reactive protein (hsCRP), glycemic and lipid profiles, blood pressure, BMI and ejection fraction were assayed. In AMI patients, blood samples were obtained at hospital admission and after 6 months, whereas coronary angiography was performed within 7 days after admission. At baseline, AMI group appeared with significantly lower ejection fraction, omentin-1 and high-density lipoprotein serum levels, whereas it had higher concentrations of white blood cells...

Translational Research, 2010

Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (C... more Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (CAD) remains obscure. In the present study, we analyzed their serum levels in patients with acute coronary syndromes (ACS) or established asymptomatic CAD. A total of 355 participants were enrolled. Among them were 80 patients with unstable angina (UA) and 115 patients with acute myocardial infarction (AMI) hospitalized in the coronary care unit. We also included 88 asymptomatic patients with established CAD (asymptomatic CAD) and 72 age-and sex-matched healthy controls (HCs). All groups with CAD underwent coronary angiography, and the Gensini score was determined. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), as well as apelin and ghrelin were assayed. Patients with ACS (UA or AMI) were sampled at hospital admission. All 3 groups with CAD (UA, AMI, or asymptomatic CAD) showed significantly higher levels of hsCRP, HOMA-IR, and white blood cells than controls (P &amp;amp;amp;amp;amp;lt; 0.01). Conversely, apelin and ghrelin concentrations were considerably (P &amp;amp;amp;amp;amp;lt; 0.05) lower in CAD patients with respect to the control group. Most importantly, UA (6.72 +/- 3.51 ng/mL) and AMI (6.02 +/- 4.07 ng/mL) groups had even lower apelin levels on admission compared with the asymptomatic CAD group (13.53 +/- 5.2 ng/mL) (P &amp;amp;amp;amp;amp;lt; 0.05). Logistic regression analysis showed an independent association of low apelin and ghrelin levels with CAD presence. Besides this result, apelin showed an inverse relationship with ACS incidence and a Gensini score independent of other cardiovascular risk factors (P &amp;amp;amp;amp;amp;lt; 0.05). In conclusion, CAD seemed to correlate with low serum apelin and ghrelin levels. Moreover, apelin concentrations inversely were associated with the severity and the acute phase of CAD, which suggests its involvement in the progression and destabilization of coronary atherosclerotic plaques.

PLoS ONE, 2014

Aim: This study aimed to investigate the effects of combined atorvastatin and exercise treatment ... more Aim: This study aimed to investigate the effects of combined atorvastatin and exercise treatment on the composition and stability of the atherosclerotic plaques in apolipoproteinE (apoE) knockout mice. Methods: Forty male, apoE 2/2 mice were fed a high-fat diet for 16 weeks. Thereafter, while maintained on high-fat diet, they were randomized into four (n = 10) groups for 8 additional weeks: Group CO: Control. Group AT: Atorvastatin treatment (10 mg/Kg/day). Group EX: Exercise-training on treadmill. Group AT+EX: Atorvastatin and simultaneous exercise training. At the study's end, plasma cholesterol levels, lipids and triglycerides were measured, along with the circulating concentrations of matrix-metalloproteinases (MMP-2,3,8,9) and their inhibitors (TIMP-1,2,3). Plaque area and the relative concentrations of collagen, elastin, macrophages, smooth muscle cells, MMP-2,3,8,9 and TIMP-1,2,3 within plaques were determined. Lastly, MMP activity was assessed in the aortic arch. Results: All intervention groups showed a lower degree of lumen stenosis, with atheromatous plaques containing more collagen and elastin. AT+EX group had less stenosis and more elastin compared to single intervention groups. MMP-3,-8-9 and macrophage intra-plaque levels were reduced in all intervention groups. EX group had increased TIMP-1 levels within the lesions, while TIMP-2 was decreased in all intervention groups. The blood levels of the above molecules increased during atherosclerosis development, but they did not change after the therapeutic interventions in accordance to their intra-plaque levels. Conclusion: The two therapeutic strategies act with synergy regarding the extent of the lesions and lumen stenosis. They stabilize the plaque, increasing its content in elastin and collagen, by influencing the MMP/TIMP equilibrium, which is mainly associated with the macrophage amount. While the increased MMP-2,-3,-8-9, as well as TIMP-1 and TIMP-2 circulating levels are markers of atherosclerosis, they are not correlated with their corresponding concentrations within the lesions after the therapeutic interventions, and cannot serve as markers for the disease development/amelioration.

Regulatory Peptides, 2011

Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. Th... more Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients. One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10-20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n=52) or lifestyle modification (LM, group, n=52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n=40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12 weeks. At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p=0.002, p=0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p=0.007) and LM group (p=0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p=0.015). On the other hand, within and between groups comparison revealed a non-significant (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;gt;0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (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;gt;0.05). In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved.

Medicine & Science in Sports & Exercise, 2010

following training. In the delayed-treatment group, there were no significant changes in any pain... more following training. In the delayed-treatment group, there were no significant changes in any pain variable between the pretest and the 8 week inactive period, but significant changes in four of the pain variables (PRIT, PRIS, PPI, NPA) after training in weeks 8-16. CONCLUSIONS: These results suggest that a progressive, whole-body weight training program has a positive impact on perception of pain in adults with Type 2 diabetes.