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Recent research reveals the crucial role microRNAs (miRNAs) in the pathogenesis and progression of many pathological conditions, including cardiovascular diseases. It is widely documented that miRNAs represent critical regulators of cardiovascular function and participate in almost all aspects of cardiovascular biology. In particular, they are involved in several pathophysiological pathways of various manifestations of cardiovascular disease, such as coronary artery disease, heart failure, stroke, diabetes mellitus, arterial hypertension and cardiac arrhythmias. In the present article we review the available literature regarding to the role of miRNAs in certain cardiovascular conditions. Moreover, we discuss the therapeutic potential of miRNAs for treating cardiovascular diseases and we attempt to highlight future directions.

Stable angina (SA) pectoris is a common and disabling disorder in patients with coronary artery disease (CAD), with increasing epidemiology and is associated with myocardial infarction and increased mortality. However, within the population of SA patients, an individual's prognosis can vary considerably. Except from conventional risk factors a variety of biomarkers have been evaluated for their prognostic significance in the settings of SA. Novel biomarkers associated with inflammatory status, such as C reactive protein and tumor necrosis factor alpha, with myocardial performance, such as B-type natriuretic peptide, with extracellular matrix remodeling, with vascular calcification such as osteoprotogerin and osteopontin, with myocardial ischemia, such as ischemia modified albumin have been associated with the progression of CAD and with the prognosis of SA patients. Despite the multiplicity of novel biomarkers there is lack of a clinical useful, highly specific for CAD biomarker with the ability to guide treatment decisions. In the context of this evidence in this review article we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors with SA physical history, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.

Introduction: Chronic aerobic exercise training is associated with favorable long term cardiovascular effects. Hypothesis: We investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE) and high intensity interval aerobic exercise (hIAE) on endothelial function, arterial stiffness and inflammatory status in healthy subjects. Methods: Twenty healthy men (mean aged 22.6±3.3yr) were recruited in this cross-over study. They participated in two exercise sessions: a) CAE: volume at 50% of maximum aerobic work on a cycle ergometer for 30 min and b) hIAE: interval maximum aerobic work on a cycle ergometer for 30 min. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery. Carotid-femoral pulse wave velocity (cfPWV) and femoral-dorsalis pedis PWV (fdPWV) were measured as indices of central aortic and peripheral arterial stiffness. Intereleukin (IL)-17 levels were measured with ELISA. Measurements were carried out before and immediately after each exercise session. Results: There was no significant differences in baseline measurements before CAE and hIAE, regarding FMD, cfPWV and fdPWV and IL-17 levels (p=NS for all). Both CAE (8.57±2.55% vs. 6.37±1.48% p Conclusions: Both CAE and hIAE can favorably affect to a similar extent endothelial function suggesting another cardioprotective effect of exercise on atherosclerosis progression. Though, these types of aerobic exercise have a different impact on central and peripheral arterial stiffness. Whether both types of exercise exert similar long-term effects merits further investigation.

Objective : Endothelial function is an independent predictor of prognosis in heart failure (HF) subjects. Statins, beyond their lipid lowering role, exert beneficial effect in patients with atherosclerosis. In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function, bone marrow-derived endothelial progenitor cells (EPC) mobilization and inflammatory status according to HF patient status. Methods : We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). The number of circulating CD34(+)/CD133(+)/KDR(+) EPCs was evaluated by flow cytometry. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery. Serum levels of tumor necrosis factor alpha (TNF-α) were measured by ELISA. Results : Treatment with atorvastatin 40 mg/d significantly increased circulating EPC ( p = 0.002), FMD ( p = 0.001) and reduced TNF-α ( p = 0.01) compared to baseline. Similarly, treatment with atorvastatin 10 mg/day increased circulating EPC ( p = 0.01), FMD ( p = 0.08) and reduced TNF-α ( p = 0.01) compared to baseline. Interestingly, with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III ( p = 0.03). Conclusions : Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects. Moreover, these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects.

Background In the present study, we evaluated the association of platelet reactivity with vascular function in patients after percutaneous coronary intervention receiving clopidogrel treatment. Methods We enrolled 150 patients with stable CAD receiving clopidogrel regimen (75mg/d), 1month after percutaneous coronary intervention. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. High on treatment platelet reactivity (HPR) was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24months. The primary end point was a composite of death from cardiovascular causes, nonfatal major cardiovascular events and hospitalization for cardiovascular causes. Results There was no difference in the basic clinical and demographic characteristics between subjects with HPR and non-HPR. Subjects with high on treatment platelet reactivity and PRU>230 had significantly increased PWV (8.81±2.25m/s vs. 7.69±1.95m/s, p =0.001) and AIx (25.27±8.67% vs. 20.87±10.57%, p =0.04) compared to subjects with PRU≤230. PWV was also associated with PRU ( r =0.23, p =0.02). HPR was associated with significantly increased risk of primary end point [HR=5.38, 95%CI:(1.15, 26.04), p =0.03]. Conclusions Increased platelet reactivity is associated with impaired arterial stiffness in patients after percutaneous coronary intervention receiving clopidogrel treatment, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy. Moreover, increased platelet reactivity is associated with adverse outcome in these patients.

Previous studies support the crucial role of immune responses in the development and progression of atherosclerosis. CD4+CD28null T cells and CD4+CD31- T cells represent two specific subsets of circulating CD4+ T cells that affect endothelium. However, their accurate role on endothelial function

Atherosclerosis is a chronic disease which mainly represents an inflammatory response in the vessels. Myocardial ischemia manifested by angina pectoris can be either acute or chronic and usually is a result of imbalance between myocardial oxygen supply and myocardial oxygen demand. Chronic stable angina is chest discomfort attributed to myocardial ischemia without the presence of necrosis and is the most common symptom encountered by emergency room physicians. A growing amount of data has shown that endothelial dysfunction, is now considered an important early event in the development of atherosclerosis, while in the absence of angiographically obstructive coronary artery disease, anginal chest pain is often attributed to microvascular coronary dysfunction. Moreover, atheroma formation and in turn, atherosclerotic plaques seem to affect coronary flow, given that multivessel flow-limiting obstructions are observed in patients with chronic coronary syndrome. Morphological changes of diseased arteries related to significant atherosclerosis, such as vascular remodeling may also result in stable angina or claudication. However, several issues with respect to the comprehension of the pathophysiology of the chronic coronary syndrome have not been fully elucidated.

T cells are involved in the process of endothelial dysfunction contributing to plaque destabilization [1] and several studies have shown that the predominant population of T cells that infiltrates atherosclerotic plaques is CD4+ T cells [2]. An increased number of CD4+ T cells have already been found in the peripheral blood of patients presenting with acute coronary syndromes [3]. Particularly, a subset of CD4+ T cells characterized by a loss of the CD31 molecule seems to have a crucial role in plaque destabilization and thrombotic complications. Furthermore, an increased number of CD4+ T lymphocytes characterized by a defective cell surface expression of CD28 have been detected in patients with unstable angina (UA). CD4+CD28null T cells were found to expand in the peripheral blood of patients with UA and infiltrate unstable coronary plaques, where they undergo clonal expansion, probably due to their activation by specific antigens [4]. Therefore, we aimed to investigate whether CD4+CD31null and CD4+CD28null T cell subpopulations contribute to vascular function in patients with UA. We enrolled 61 patients with UA admitted to our Coronary Care Unit with UA Braunwald's class IIIB and 23 healthy individuals without overt cardiovascular disease who were screened in our outpatients' clinic for cardiovascular prevention. Endothelial function was evaluated by estimating the flow-mediated dilation (FMD) in the brachial artery, while flow cytometry was used to determine both the number of T-cells present as well as the frequencies of the various T-cell subsets of interest. We have found that endothelial function was significantly impaired in patients with UA compared to healthy controls (4.76 ± 0.24 vs 8.4 ±0.52, p b 0.001, Fig. 1A), while further analysis among the genders of the 2 groups did not reveal any significant differences in FMD (p = 0.631 for males and p= 0.767 for females). Similarly, FMD was not age related. More specifically, after dividing patients into two subgroups according to age, using as a cut-off point the age of 60 years, we observed no significant differences (p = 0.453 and p = 0.562 respectively). Importantly, we have shown that T cell population as marked by CD4+ was elevated in UA patients compared to healthy controls (42.07 ± 1.58 vs 35.43 ± 3.1, p = 0.046). Interestingly, a significant difference was detected between the two groups when the T cell subpopulation CD4+CD31null was examined. A significant increase of these circulating cells were found in the UA group (37.33 ± 1.5 vs 28.98 ± 3.1, p = 0.016, Fig. 1B). Similarly, UA patients presented with a significantly elevated frequency of CD4+CD28null T cells (9.49 ± 0.69 vs 6.69 ± 1.19, p = 0.018, Fig. 1C). However, no significant difference between groups was observed in the frequency

Chronic exercise training improves endothelial function in individuals with cardiovascular diseases. Endothelial function and arterial stiffness are key players in the pathophysiology of atherosclerotic disease. We investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE

Purpose: The role of CYP2C19*2 polymorphism in plasma clopidogrel active drug metabolite concentrations, in platelet inhibition and in cardiovascular prognosis has come under question in recent studies. We examined the impact of functional genetic polymorphism CYP2C19*2 on endothelial function and arterial stiffness in patients with CAD treated with clopidogrel regimen. Methods: We consecutively enrolled 408 patients with stable CAD receiving clopidogrel regimen (75mg/d), one month after percutaneous coronary intervention. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. CYP2C19*2 genotyping was performed by real-time polymerase chain reaction. High on treatment platelet reactivity was evaluated using VerifyNow Assay. VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230 PRU. Results: From the study population 150 patients (36.8%) were carriers of at least one CYP2C19*2 reduced-function allele and 258 patients (63.2%) were non carriers. There was no statistically significant difference between carriers and non carriers in age, male sex and the presence of hyperlipidemia, diabetes mellitus, arterial hypertension, in smoking habits, in anticoagulant and statin treatment. Importantly, there was no difference in FMD (4.88±2.34% vs. 4.83±2.21%, p=0.83), PWV (8.53±2.54m/sec vs. 8.85±2.33m/sec, p=0.19) and AIx values (22.87±10.04% vs. 23.82±8.43%, p=0.31) between carriers and non carriers respectively. Finally, carriers of two CYP2C19*2 reduced-function allele had significantly increased PRU (292±53 vs. 198±83, p=0.007). Conclusions: The presence of CYP2C19*2 loss of action polymorphism displays no impact on arterial wall properties in patients with CAD treated with clopidogrel regimen. Moreover, carriers of two CYP2C19 reduced-function alleles had significantly increased platelet reactivity.

Diabetes Mellitus is associated with endothelial dysfunction and arterial stiffness. Diabetic Retinopathy (DR) is a complication of diabetes mellitus and remains a leading cause of irreversible blindness. We investigated the possible association of DR with endothelial function, arterial stiffness

Background: Patients with heart failure (HF) have a significant decline of renal function. We investigate the association between novel biomarkers of renal dysfunction and indices of inflammatory status and cardiac remodeling in patients with HF. Methods: We enrolled 79 consecutive patients with HF and 79 healthy subjects, adjusted for age and sex. Serum levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, b-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNFα) and matrix metalloproteinase-9 (MMP-9) were measured by ELISA. Creatinine clearance was estimated using Cockcroft-Gault formula (eCcl). Left ventricular ejection fraction was determined by echocardiography. Results: Patients with HF, compared to healthy subjects, had significantly higher NGAL (p=0.007) and cystatin-C levels (p=0.005). In HF patients, NGAL levels were positively correlated with Creatinine levels (r=0.40, p