Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

Abstract

Left ventricular hypertrophy and microRNAsLeft ventricular hypertrophy (LVH) can be elicited by several clinical conditions, including systemic hypertension, cardiac valve disease, and myocardial infarction, that increase cardiac workload. This adaptation is one facet of cardiac remodeling and subsequent heart failure (HF), which is a major cause of death in Western countries (1). In 1970, the Framingham Heart Study revealed that the presence of LVH alone is associated with increased mortality (1). Moreover, recent appraisals of this cohort have also linked LVH to arrhythmic sudden cardiac death (2). Interestingly, inhibition of LVH after transverse aortic constriction prevents HF and increases survival in genetically modified animals (3, 4).Because of the strong correlation between LVH and sudden cardiac death, the mechanisms underlying LVH etiology, and degeneration toward HF, have been studied extensively (4, 5). Several aspects of LVH-dependent HF still need to be clarified, and, in this regard, microRNAs (miRs) could provide additional insights into the mechanisms involved in LVH and HF. miRs are short (17-25 nucleotides) Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, was identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes. These advanced comprehensive analyses represent a major step forward in our understanding of cardiovascular physiopathology, providing a promising adjunctive target for possible therapeutic approaches, namely the miRmediated paracrine signaling network.

Transcoronary concentration gradients of circulating microRNAs in heart failure

“…it mediates cell-to-cell communications between fibroblasts and cardiomyocytes. 33 To this regard, in the present study, CVS levels of miR-21-3p were significantly correlated with multiple parameters of left ventricular function, such as LVEF, end-diastolic and end-systolic diameters. Also in line with our findings, lower circulating levels of miR-126 had been reported in HF patients, where its levels were correlated with age, left ventricular function, NT-proBNP levels, and left atrial volume.…”

Pathologic function and therapeutic potential of exosomes in cardiovascular disease

“…Moreover, the ability of exosomes to transfer lipid, RNA, and proteins raises very exciting possibilities for future therapeutic uses. For example, based on the regulatory effects of miR on therapeutic proteins [132, 133], we could engineer host cells to overexpress a specific miR that is capable to be delivered via exosomes. These engineered cells can be either encapsulated to provide sustained local delivery or utilized as “factory” to produce therapeutic exosomes.…”

Exosomal miRNAs in Heart Disease

“…It has been shown that miRNAs are aberrantly expressed in the cardiovascular system under some pathological conditions, including myocardial infarction (19,45), heart failure (6,77), cardiac hypertrophy (36,44), and proliferative thickening of the vessel known as restenosis (15,55).…”