MicroRNAs: roles in cardiovascular development and disease

Highlights

• A strong evidence illustrates that heart pathological processes are mostly resulted from genetic components and alterations in their expressions’ profiles, as momentous for heart function.

• MicroRNAs, as dynamic switches, are not only capable to regulate the gene expression, but they can also fine-tune the biological processes involved in genetic basis, occurrence, diagnosis, and prognosis of cardiovascular diseases.

• The knowledge on that microRNA expression is frequently dysregulated in cardiovascular diseases, has uncovered an entirely new repertoire of molecular factors’ upstream of gene expression, with an exciting potential as a novel biomarker as well as a therapeutic target.

Abstract

Cardiovascular diseases (CVDs) comprise a group of disorders ranging from peripheral artery, coronary artery, cardiac valve, cardiac muscle, and congenital heart diseases to arrhythmias and ultimately, heart failure. For all the advances in therapeutics, CVDs are still the leading cause of mortality the world over, hence the significance of a thorough understanding of CVDs at the molecular level. Disparities in the expressions of genes and microRNAs (miRNAs) play a crucial role in the determination of the fate of cellular pathways, which ultimately affect an organism's physiology. Indeed, miRNAs serve as the regulators of gene expressions in that they perform key functions both in several important cellular pathways and in the regulation of the onset of various diseases such as CVDs. Many miRNAs are expressed in embryonic, postnatal, and adult hearts; their aberrant expression or genetic deletion is associated with abnormal cardiac cell differentiation, disruption in heart development, and cardiac dysfunction. A substantial body of evidence implicates miRNAs in CVD development and suggests them as diagnostic biomarkers and intriguing therapeutic tools.

The present review provides an overview of the history, biogenesis, and processing of miRNAs, as well as their function in the development, remodeling, and diseases of the heart.

Introduction

Cardiovascular diseases (CVDs) are regarded as the major cause of human mortality worldwide. CVDs are progressive and complex diseases and include familial hypercholesterolemia, cardiomyopathies, congenital heart diseases (CHD), thoracic aortic aneurysms, coronary artery disease, and heart failure [1]. The prognosis of CVDs is still poor despite improvements in their outcome and survival owing to developments in pharmacological and surgical armamentaria [2].

A considerable body of evidence indicates that cardiac pathological processes mostly result from genetic components and alterations in their expression profile [3]. The past few decades have witnessed the introduction of microRNAs (miRNAs) as some of the most significant molecular targets in studies on the mechanisms of CVDs and the management of their symptoms. Approximately, 2300 mature miRNAs genes have been reported to exist in the human [4]. Lin-4 was the first miRNA discovered in Caenorhabditis elegans by Victor Ambros et al in 1993. However, what significantly drew the attention of biologists to miRNAs was the identification of the Let-7 miRNA by Gary Ruvkun et al in 2001. Functional studies have shown the involvement of miRNAs in a diverse range of cellular biological processes such as development, cycle regulation, proliferation, differentiation, apoptosis, and angiogenesis, as well as the responses of the immune and cardiovascular systems to pathogens and cancers [[5], [6], [7]].

Translational research is aimed at building on basic scientific research to create novel diagnostic modalities and therapies. By way of example, the analysis of miRNA function during the development of the cardiovascular system could confer novel miRNA-based therapeutic strategies. To that end, in the current study, we present an overview of the latest findings on the role of miRNA regulation in cardiac development.