MicroRNAs in Cardiovascular Therapeutics

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

Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients

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-alpha) 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-alpha (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-alpha (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. (C) 2014 Elsevier Ireland Ltd. All rights reserved

High platelet reactivity is associated with vascular function in patients after percutaneous coronary intervention receiving clopidogrel

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 (75 mg/d), 1 month 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 Verify Now Assay. Verify Now reports its results in P2Y12 reaction units (PRU), and the diagnostic cutoff value is 230 PRU. Patients were evaluated prospectively up to 24 months. 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 +/- 2.25 m/s vs. 7.69 +/- 1.95 m/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. (C) 2014 Elsevier Ireland Ltd. All rights reserved