Characterization of Systemic and Culprit-Coronary Artery miR-483-5p Expression in Chronic CAD and Acute Myocardial Infarction Male Patients.

Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area. Blood from chronic-CAD, acute-MI with/out ST segment elevation (STEMI/NSTEMI, respectively), and control patients lacking previous CAD or having patent coronary arteries was collected during coronary catheterization from peripheral arteries and from proximal culprit coronary arteries aimed for the interventions. Random coronary arterial blood was collected from controls; RNA extraction, miRNA library preparation and Next Generation Sequencing followed. High concentrations of microRNA-483-5p (miR-483-5p) were noted as 'coronary arterial gradient' in culprit acute-MI versus chronic-CAD (p = 0.035) which were similar to controls versus chronic-CAD (p < 0.001). Meanwhile, peripheral miR-483-5p was downregulated in acute-MI and chronic-CAD, compared with controls (1.1 ± 2.2 vs. 2.6 ± 3.3, respectively, p < 0.005). A receiver operating characteristic curve analysis for miR483-5p association with chronic CAD demonstrated an area under the curve of 0.722 (p < 0.001) with 79% sensitivity and 70% specificity. Using in silico gene analysis, we detected miR-483-5p cardiac gene targets, responsible for inflammation (PLA2G5), oxidative stress (NUDT8, GRK2), apoptosis (DNAAF10), fibrosis (IQSEC2, ZMYM6, MYOM2), angiogenesis (HGSNAT, TIMP2) and wound healing (ADAMTS2). High miR-483-5p 'coronary arterial gradient' in acute-MI, unnoticed in chronic-CAD, suggests important local mechanisms for miR483-5p in CAD in response to local myocardial ischemia. MiR-483-5p may have an important role as a gene modulator for pathologic and tissue repair states, is a suggestive biomarker, and is a potential therapeutic target for acute and chronic cardiovascular disease.

Differential microRNAs expression in calcified versus rheumatic aortic valve disease.

BACKGROUND: The aortic valve (AV) is the most commonly affected valve in valvular heart diseases (VHDs). The objective of the study is to identify microRNA (miRNA) molecules expressed in VHDs and the differential expression patterns of miRNA in AVs with either calcification or rheumatism etiologies. METHODS: Human AVs were collected during valve replacement surgery. RNA was extracted and miRNA containing libraries were prepared and sequenced using the next generation sequencing (NGS) approach. miRNAs identified as differentially expressed between the two etiologies were validated by quantitative real-time polymerase chain reaction (qPCR). The receiver operating characteristic (ROC) curve analysis was performed to examine the ability of relevant miRNA to differentiate between calcification and rheumatism etiologies. RESULTS: Rheumatic and calcified AV samples were prepared for the NGS and were successfully sequenced. The expression was validated by the qPCR approach in 46 AVs, 13 rheumatic, and 33 calcified AVs, confirming that miR-145-5p, miR-199a-5p, and miR-5701 were significantly higher in rheumatic AVs as compared with calcified AVs. ROC curve analysis revealed that miR-145-5p had a sensitivity of 76.92% and a specificity of 94.12%, area under the curve (AUC) = 0.88 (P = .0001), and miR-5701 had a sensitivity of 84.62% and a specificity of 76.47%, AUC = 0.78 (P = .0001), whereas miR-199a-5p had a sensitivity of 84.62%, and a specificity of 57.58%, AUC = 0.73 (P = .0083). CONCLUSION: We documented differential miRNA expression between AV disease etiologies. The miRNAs identified in this study advance our understanding of the mechanisms underlining AV disease.

Cardiac-peripheral transvenous gradients of microRNA expression in systolic heart failure patients.

AIMS: The aims of the study are to assess the levels of coronary sinus (CS) miRNAs of systolic heart failure (HF) patients in samples obtained during cardiac resynchronization therapy (CRT) device implantation and compare them to the peripheral systemic venous miRNA expression. METHODS AND RESULTS: The cardiac specific miRNA levels were assessed in 60 patients, 39 HF patients with reduced ejection fraction and 21 control patients. The levels of four cardiac specified miRNAs (miR-21-5p, miR-92b-3p, miR-125b-5p, and miR-133a-3p) were compared between the peripheral samples of HF and controls and between peripheral venous in CS in the HF groups. Compared with controls, HF patients had higher peripheral serum venous levels of miR-125b-5p and miR-133-3p. In the HF group, the levels of expression were higher for miR-125b-5p and lower for miR-92, and miR-21-5p in the CS, compared with the peripheral venous circulation. CONCLUSIONS: The differences in miRNA expressions in CS compared with those in the periphery suggest that changes that may occur at the levels of the myocardial tissue in HF may be more relevant to our understanding of the biological linkage between miRNA expression and HF, than the traditional analysis of systemic serum miRNA expression.