Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease

Abstract

MicroRNAs (miRNAs) comprise a class of small, noncoding RNAs that control expression of complementary target mRNAs. Dysregulation of intracellular miRNA expression has been described in various diseases, including a number of cardiovascular conditions. Functional studies have shown a role for miRNAs in cardiac fibrosis, hypertrophy, angiogenesis, and heart failure.1,–,3 These findings suggest a new therapeutic entry point for cardiac disease and illustrate the broad therapeutic potential of miRNA modulation. Initial reports have detected circulating extracellular miRNAs in the serum/plasma of patients with cancer.4 Despite the existence of RNases, miRNAs remain stable in serum and other body fluids. One explanation is the inclusion of miRNAs into lipid or lipoprotein complexes such as exosomes5 or microvesicles.6 Subsequently, altered concentrations of miRNAs have been found in patients with various cardiovascular diseases. Here, we review the current knowledge about circulating miRNAs during coronary artery disease (CAD), myocardial infarction, and heart failure (Table). A further new and exciting function of circulating miRNAs in the cardiovascular system may be their potential to serve as paracrine signaling molecules.7 The detection of circulating miRNAs in serum/plasma8,9 suggests that miRNAs may fulfill biological functions outside the cell and serve as potential biomarkers for diseases. Circulating miRNAs are protected from RNase-dependent degradation by several mechanisms, including their inclusion in microvesicles, exosomes, and apoptotic bodies as well as through the formation of protein-miRNA complexes resistant to degradation (Figure). In addition, circulating miRNAs are quite stable even after multiple freeze-thaw cycles.8 Recent studies have shown that miRNAs are actively secreted in microvesicles or exosomes from different cell types.6,10 Despite the current knowledge about the existence of circulating miRNAs and the intercellular transfer of miRNAs from donor …