Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease

Abstract

MicroRNAs (miRNAs) are short sequences of non-coding RNA that play an important role in the regulation of gene expression and thereby in many physiological and pathological processes. Furthermore, miRNAs are released in the extracellular space, for example in vesicles, and are detectable in various biological fluids, such as serum, plasma, and urine. Over the last years, it has been shown that miRNAs are crucial in the development of several cardiovascular diseases (CVDs). This review discusses the (patho)physiological implications of miRNAs in CVD, ranging from cardiovascular risk factors (i.e., hypertension, diabetes, dyslipidemia), to atherosclerosis, myocardial infarction, and cardiac remodeling. Moreover, the intriguing possibility of their use as disease-specific diagnostic and prognostic biomarkers for human CVDs will be discussed in detail. Finally, as several approaches have been developed to alter miRNA expression and function (i.e., mimics, antagomirs, and target-site blockers), we will highlight the miRNAs with the most promising therapeutic potential that may represent suitable candidates for therapeutic intervention in future translational studies and ultimately in clinical trials. All in all, this review gives a comprehensive overview of the most relevant miRNAs in CVD and discusses their potential use as biomarkers and even therapeutic targets.

Keywords: atherosclerosis; biomarker; cardiac remodeling; cardiovascular diseases; cardiovascular risk factors; microRNAs; myocardial infarction; therapy.

FIGURE 1

MicroRNAs in cardiovascular risk factors. The miRNAs involved in the pathogenesis of dyslipidemia, diabetes and hypertension are shown in the inner yellow, green, and red circles, respectively. In the outer circles the miRNAs are listed which have been studied as biomarker. Moreover, the therapeutically targeted miRNAs are shown in blue circles and their initial effect on the cardiovascular risk factors is depicted as a black, stimulatory or inhibitory arrow. The green circles indicate the method of intervention and their effect on the miRNA is visualized as a red, stimulatory or inhibitory arrow.

FIGURE 2

MicroRNAs in atherosclerosis. MiRNAs involved in the pathogenesis of atherosclerosis are grouped per cell type (i.e., endothelial cells, vascular smooth muscle cells, and macrophages and monocytes). The (–), (+), and (–/+) indicate that the miRNA is either atheroprotective, pro-atherogenic or both, respectively. Additionally, circulatory biomarker miRNAs are listed in the red box. Furthermore, the miRNAs that have been studied as therapeutic target are depicted in blue circles and their initial effect on atherosclerosis is shown as a black, stimulatory or inhibitory arrow. The therapeutic intervention is shown in green circles and the effect on the miRNA is depicted as a red, stimulatory or inhibitory arrow.

FIGURE 3

MicroRNAs in myocardial infarction. MiRNAs involved in the pathogenesis of myocardial infarction are grouped per cell death type (i.e., apoptosis and necrosis). Moreover, the circulatory miRNAs studies as biomarker are listed in the red box. Furthermore, the therapeutically targeted miRNAs are visualized in blue circles and their initial effect on myocardial infarction is shown as a black, stimulatory or inhibitory arrow. The therapeutic intervention is depicted in green circles and their effect on the targeted miRNA is shown as a red, stimulatory or inhibitory arrow.

FIGURE 4

MicroRNAs in cardiac remodeling. The miRNAs involved in the pathogenesis of cardiac fibrosis and hypertrophy are visualized in the inner green and yellow circles, respectively. The miRNAs which have been studied as biomarker are listed in the outer circles. Additionally, the miRNAs studied as therapeutic are shown in blue circles and their initial effect on the pathologies is visualized as a black, stimulatory or inhibitory arrow. The method of intervention is depicted in the green circles and their effect on the miRNA target is shown as a red, stimulatory or inhibitory arrow.