Effect of pathological conditions and exercise training on microRNA
MicroRNAs (miRNAs) are endogenous, single-stranded, small, ~22-nucleotide noncoding RNAs, which are generally regarded as negative regulators of gene expression by inhibiting translation and/or promoting mRNA degradation by base pairing to complementary sequences within the 3′ untranslated region (3′UTR) of protein-coding mRNA transcripts.
During pathological processes of the heart the expression profile of genes are altered. The regulation of cardiac gene expression is complex, with individual genes controlled by multiple enhancers that direct very specific expression patterns in the heart. The pathological processes of cardiovascular system (heart failure and several CVD) are associated with a specific signature pattern of miRNA (Thum, Galuppo et al. 2007).
Myocardial infarction: Acute myocardial infarction is a complex process in which multiple genes have been found to be dysregulated. Ren et al. applied a mouse model of cardiac ischemia-reperfusion (I/R) in vivo and ex vivo to determine the miRNA expression signature in ischemic hearts, and found that miR-320 expression was consistently dysregulated in ischemic hearts (Ren, Wu et al. 2009).
Recently, circulating miRNAs are reported in patients with myocardial infarction. Wang et al. found that circulating miR-208a may be a novel biomarker for early detection of myocardial injury in human (Wang, Zhu et al. 2010). It has been hypothesized that miRNAs in systemic circulation may reflect tissue damage, and for this reason, they can be used as a biomarker of myocardial infarction.
Pathological hypertrophy: Pathological hypertrophy is mainly caused by hypertension, loss of myocytes following ischemic damage, and genetic alterations that cause cardiomyopathy. Moreover, metabolic abnormality or stress can also lead to hypertrophy. In animal models of cardiac hypertrophy, whole arrays of miRNAs have indicated that separate miRNAs are upregulated, downregulated, or remain unchanged with respect to their levels in a normal heart. miR-21, miR-23a, miR-24, miR-125, miR-129, miR-195, miR-199, miR-208, and miR-212 have often been found to be upregualted with hypertrophy, whereas miR-1, miR-133, miR-29, miR-30, and miR-150 have often been found to be downregualted.
Effects of exercise on miRNAs: Fish et al. demonstrated that miR-29 is involved in the improvement of ventricular compliance and this is promoted by aerobic ET due to a modulation of decreased collagen synthesis in cardiac fibroblasts (Soci, Fernandes et al. 2011). With respect to the regulation of eNOS activity by increased shear stress, evidence from cell-culture experiments documented an involvement of miRNA-21 where overexpression of the former resulted in an activation of eNOS and a 3.7-fold increased NO production, yet inhibition of miRNA-21 abolished the shear-induced activation of eNOS (Weber, Baker et al. 2010).