Panagiotis Konstantopoulos

Correlation between mesenteric fat thickness and serum apolipoproteins in patients with peripheral arterial occlusive disease

BackgroundVisceral fat possesses the most detrimental potential for cardiovascular morbidity through the release of adipokines, as well as metabolic and proinflammatory mediators, which adversely affect metabolic and vascular homeostasis. Among the different types of visceral adipose tissue, mesenteric fat is considered particularly detrimental, due to its close proximity to the portal circulation, affecting directly the liver, which is the main regulator of body metabolic homeostasis. Mesenteric fat can be reliably estimated using abdominal ultrasonography, the only available imaging method able to depict individual mesenteric leaves. Aim of the present study was to investigate the correlation of mesenteric fat thickness (MFT) with serum apolipoprotein levels in patients undergoing digital subtraction angiography in a single center.Methods35 male patients with peripheral arterial disease were examined. After careful examination of the periumbilical area, the mesenteric leaves were identified. The maximal distance between each pair of sequential leaves was measured, and the mean value of the three thickest leaves was determined as the mesenteric fat thickness. Six apolipoprotein fasting serum concentrations were measured using a Luminex proteomics platform (xMAP Multiplex immunoassay): apolipoprotein A-I (apoAI), apolipoprotein A-II (apoAII), apolipoprotein B (apoB), apolipoprotein C-II (apoCII), apolipoprotein C-III (apoCIII) and apolipoprotein E (apoE).ResultsMFT correlated with apoAII and apoB serum concentrations. The correlations with apoAII and apoB remained significant following correction for BMI. No correlations were noted between MFT and serum apoAI, apoCII, apoCIII or apoE levels before or after adjustment for BMI.ConclusionsOur study indicates that MFT is significantly correlated with the concentration of atherogenic low density lipoproteins particles, as well as with apoAII, a determinant of free fatty acids levels. No correlation was observed between mesenteric fat thickness and very low density lipoprotein or chylomicron particles concentration.

Short Leukocyte Telomere Length Precedes Clinical Expression of AtherosclerosisNovelty and Significance: The Blood-and-Muscle Model

Rationale: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue. Objective: We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. Methods and Results: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. Conclusions: This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941.

MANAGEMENT OF ENDOCRINE DISEASE: The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis

OBJECTIVE Subclinical hypothyroidism (SCH) is encountered in 10-25% of women with PCOS. To date, it remains unclear whether this coexistence influences the severity of metabolic and hormonal profile of these patients. The purpose of our systematic review is to investigate this potential relation. METHODS We systematically searched Medline, Scopus, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases together with reference lists from included studies. All prospective and retrospective observational cohort studies that investigated the impact of subclinical hypothyroidism on hormonal and metabolic parameters of PCOS patients were included. The methodological quality of studies was assessed with the Ottawa-Newcastle criteria. Statistical meta-analysis was performed with the RevMan 5.3 software. RESULTS Twelve studies were finally included in the present review, which enrolled 2341 PCOS patients. Among them, 577 had subclinical hypothyroidism, whereas the remaining 2077 were PCOS women with normal thyroid function. The presence of SCH significantly affected HDL (MD -3.92 mg/dL 95% CI: -6.56, -1.29) and triglycerides levels (26.91 mg/dL 95% CI: -3.79, 50.02). HOMA-IR was also affected (MD 0.82 95% CI: 0.15, 1.50). On the other hand, LDL, fasting glucose and 2-h OGTT were not influenced. Similarly, prolactin, FSH, LH, LH/FSH ratio and sex hormone-binding globulin remained unaffected. CONCLUSION Subclinical hypothyroidism does not influence the hormonal profile of women with PCOS. On the other hand, it results in mild metabolic abnormalities, which are not clinically important in a short-term setting.

A sirtuin 1/MMP2 prognostic index for myocardial infarction in patients with advanced coronary artery disease

BACKGROUND Sirtuin 1 (SIRT1) appears to play a protective role against endothelial dysfunction and oxidative stress. Instead, matrix metalloproteinase 2 (MMP2) is involved in acute coronary events, by promoting tissue remodeling. This study sought to determine the clinical value of a prognostic index arising from the combination of these two biomarkers for myocardial infarction (MI) in patients with advanced coronary artery disease. METHODS Eighty-one patients with advanced coronary artery disease planned for open heart surgery were prospectively enrolled. Serum levels of SIRT1 and MMP2 were measured by ELISA. To look at the relation of these mediators with clinical characteristics, pre-operative data and patients demographics were collected. RESULTS SIRT1 levels correlated marginally with a history of hypertension (ρ=0.2, p=0.084) and inversely with baseline urea (ρ=0.25, p=0.056). When performing additional adjustment, low SIRT1 levels were independently associated with diabetes mellitus 2(DM2) and subjects with SIRT1 <2.95ng/mL were more prone to present DM2 (82% sensitivity and 62% specificity). The index of low SIRT1 and high MMP2 respectively correlated with patients history of MI (ρ=0.3, p=0.01) and marginally with presence or history of atrial fibrillation (AF) (ρ=0.213, p=0.076). When adjusting for anthropometric and comorbidities, the combined index tended to have an association with impaired ejection fraction (EF)<55% (p=0.059). CONCLUSIONS The combined index of low SIRT1 and high MMP2 exhibited a significant correlation with history of MI and EF, promoting a potential prognostic tool for MI incidence in patients regardless their coronary artery disease status.

Protective effects of N-acetylcystein and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion

AIM OF THE STUDY We sought to examine whether the separate and combined effect of N-acetylcystein (NAC) and atorvastatin prevented hepatic and renal tissue injury induced by intestinal ischemia-reperfusion (I/R). MATERIAL AND METHODS 40 male Wistar rats were allocated into 5 experimental groups; Control (n=8): sham, I/R (n=8): rats underwent occlusion of superior mesenteric artery for 45min, Atorvastatin (n=8): rats received 10mg/kg atorvastatin, NAC (n=8): rats received 160mg/kg NAC, NAC&Atorvastatin (n=8): rats received both aforementioned agents. Administration of the agents was facilitated by oral gavage 24h before I/R. Serum levels of urea, creatinine, transaminases, IL-1β, IL-6, TNF-α, ICAM-1, as well as liver and kidney histopathological examination were evaluated. RESULTS Pretreatment with either NAC or Atorvastatin or their combination led to lower levels of transaminases and ICAM-1 (2.75±0.46, 2.88±0.84 and 1.5±0.76 respectively for NAC, Atorvastatin and I/R groups), while only their combination led to lower ratios of IL-1, IL-6 and TNF-α than I/R group (1.3±0.12 vs 1.94±0.54, 1.21±0.11 vs 2.12±0.96 and 1.33±0.11 vs 2.14±0.77, respectively). NAC was associated with enhanced renal tissue histology, while atorvastatin was found superior in protecting hepatic tissue degenaration. CONCLUSIONS Both agents, seperately and combined, seem to exhibited tissue-specific protective activity against intestinal I/R induced injury.

Metabolic effects of Crocus sativus and protective action against non-alcoholic fatty liver disease in diabetic rats

Non-alcoholic fatty liver disease (NAFLD) is the result of the accumulation of adipose tissue deposits in the liver and it is associated with type 2 diabetes. Crocus sativus (saffron) is known for its antioxidant and its potential hypoglycemic effects. We investigated the role of saffron on NAFLD in diabetic rats. Thirty adult male rats were allocated into three groups; control (n=10), which received normal diet; streptozotocin (STZ) group (n=10), which received normal chow diet, 10% fructose in their drinking water and STZ (40 mg/kg body weight; STZ-saffron group (n=10), which followed the same dietary and pharmacological pattern as STZ group and were additionally supplemented with saffron (100 mg/kg/day). Metabolic profile was measured and histopathological examination of the liver was evaluated. STZ group exhibited the highest glucose levels at the end of the experiment (P<0.05), while there was no difference between control and STZ-saffron group (584 vs. 213 mg/dl vs. 209 mg/dl, respectively). STZ group revealed higher percentage of steatosis (5–33%) when compared to the other two groups (P<0.005). Saffron exhibits both hypoglycemic and hepatoprotective actions. Yet, further studies enlightening the exact mechanisms of saffrons mode of actions are required.

Pre-treatment with simvastatin prevents the induction of diet-induced atherosclerosis in a rabbit model

The aim of the present study was to investigate the potential antiatherosclerotic activities of simvastatin in rabbits. Twenty-two, male, New Zealand rabbits were divided into the following groups: Control group (group C); cholesterol group (group A), in which the rabbits were fed a commercial rabbit chow supplemented with 0.5% w/w cholesterol for 8 weeks and then fed with normal chow for an additional 8 weeks; and a treatment group (group B), in which the rabbits initially received standard commercial rabbit chow along with being administered simvastatin for 8 weeks, following which they consumed a high-cholesterol diet for a further 8 weeks. The rabbits pre-treated with simvastatin presented significantly lower serum cholesterol and low-density lipoprotein cholesterol levels when compared with the non simvastatin-treated cholesterol-fed animals. Furthermore, none of the rabbits in the simvastatin group presented with atherosclerotic lesions in the aorta. Thus, simvastatin was demonstrated to exhibit preventive properties against the formation of atherosclerosis in the atherosclerosis model in the current study, predominantly via its hypolipidemic activity.

Effect of Saffron on Metabolic Profile and Retina in Apolipoprotein E–Knockout Mice Fed a High-Fat Diet

ABSTRACT Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE −/− mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE −/− mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE −/− mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water. The duration of the study was 20 weeks. Lipidemic profile, glucose, C-reactive protein (CRP), and total oxidative capacity (PerOX) were measured in blood serum. Histological analysis of retina was also conducted. Administration of saffron resulted in enhanced glycemic control and preservation of retinal thickness when compared with apoE −/− mice fed a high-fat diet. The outcomes of the study suggest the potential protective role of saffron against retinal damage induced by oxidative stress. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.

Proteomic profile of patients with atrial fibrillation undergoing cardiac surgery

OBJECTIVES Proteomic analysis of patients with advanced cardiovascular disease was conducted to identify possible biomarkers for atrial fibrillation (AF). METHODS A total of 123 patients undergoing cardiac surgery (22 with AF and 101 without AF) and 20 healthy subjects were recruited. Demographic data, patient history and blood samples were collected. Growth/differentiation factor 15, resistin, intracellular adhesion molecule-1, galectin-3, trefoil factor 3, tissue inhibitor of metalloproteinases 1, matrix metallopeptidase 9, high-sensitive troponin T, interleukins 6, 1α, 3, 4, 8, 20 and 22, tumour necrosis factor alpha, C-X-C motif chemokines 10 and 11, S100A6 and Type III procollagen were measured in blood serum. Differential expression between any 2 groups for any of the measured proteins was identified by fitting linear models, whereas Matthews Correlation Coefficient was used to evaluate their predictive capacity. Combined markers using more than 1 protein were attained via weighted Support Vector Machines. RESULTS Although serum levels of the markers were higher in patients with cardiovascular disease than in healthy subjects, only growth/differentiation factor 15 and resistin were significantly higher in patients with AF among the subpopulation who underwent heart surgery (P = 0.029 and P = 0.007, respectively). Specific pairs of several biomarkers had mediocre predictive capacity for AF. CONCLUSIONS Growth/differentiation factor 15 and resistin are 2 markers that could be helpful in stratifying risk for AF in patients with cardiovascular disease. Yet, more research in terms of proteomics and investigation of possible molecular pathways implicated is required.

Chios mastic gum decreases renin levels and ameliorates vascular remodeling in renovascular hypertensive rats

Chios mastic gum (CMG) exerts robust anti-inflammatory and antioxidant properties and it affects pathways that are implicated in the pathophysiology of endothelial and vascular inflammation. Aim of this study was to test the hypothesis that CMG administration lowers blood pressure (BP) and improves hypertension-induced target organ damage. 2-kidney, 1-clip (2K1C) hypertensive rats were treated with CMG (40 mg/kg body weight/day) for 2-weeks after the establishment of hypertension. Acute CMG administration lowered systolic, diastolic and mean arterial BP, while these hemodynamic effects were sustained throughout the 2-week administration period. CMG group also exhibited alleviated target organ damage as proposed by amelioration of biomechanical properties of the aorta -including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. The anti-hypertensive effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis indicated that the effect of CMG on organ damage was BP-lowering dependent and was not associated with direct effects of renin or with its anti-inflammatory properties. We suggest a BP lowering effect of CMG via down-regulation of renin excretion associated with attenuation of target organ damage and inflammatory status. These observations provide profound evidence for the beneficial role of CMG in hypertension, which could possibly translate to further clinical research.