Abstract

Cardiovascular diseases (CVDs) are still the main cause of morbidity and mortality worldwide and include a group of disorders varying from vasculature, myocardium, arrhythmias and cardiac development. MicroRNAs (miRs) are endogenous non-coding RNAs with 18–23 nucleotides that regulate gene expression. The miR-34 family, including miR-34a/b/c, plays a vital role in the regulation of myocardial physiology and pathophysiological processes. Recently, miR-34a has been implicated in cardiovascular fibrosis, dysfunction and related cardiovascular disorders as an essential regulator. Interestingly, there is a pivotal link among miR-34a, cardiovascular fibrosis, and Smad4/TGF-β1 signaling. Notably, both loss-of-function and gain-of-function approaches identified the critical roles of miR-34a in cardiovascular apoptosis, autophagy, inflammation, senescence and remodeling by modulating multifunctional signaling pathways. In this article, we focus on the current understanding of miR-34a in biogenesis, its biological effects and its implications for cardiac pathologies including myocardial infarction, heart failure, ischaemia reperfusion injury, cardiomyopathy, atherosclerosis, hypertension and atrial fibrillation. Thus, further understanding of the effects of miR-34a on cardiovascular diseases will aid the development of effective interventions. Targeting for miR-34a has emerged as a potential therapeutic target for cardiovascular dysfunction and related diseases.

Highlights

  • Cardiovascular diseases (CVDs) are regarded as the leading cause of human death worldwide [1]

  • MiR-34a-5p was found to be elevated in human coronary artery endothelial cells (HCAECs) exposed to chronic intermittent hypoxia (CIH), further increasing autophagy-related proteins such as Beclin and LC3. These results indicated that miR-34a-5p contributed to CIH-induced HCAECs autophagy through Bcl2/Beclin signaling pathways

  • The roles of miRs in I/R injury are mediated through the regulation of essential signaling pathways involved in necrosis, apoptosis, oxidative stress, inflammation, fibrosis and angiogenesis [77]

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Summary

Introduction

Cardiovascular diseases (CVDs) are regarded as the leading cause of human death worldwide [1]. ALDH2, Aldehyde dehydrogenase 2; Anf, atrial natriuretic factor; ApoE–/–, Apolipoprotein E-defcient; α-SMA, α-smooth muscle actin; bFGF, Basic fibroblast growth factor; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2 associated X protein; CAVS, Calcific aortic valve stenosis; CAT, catalase; CMECs, Cardiac microvascular endothelial cells; DOXO, doxorubicin; EF, ejection fraction; ER, Endoplasmic reticulum; FS, fractional shorting; GSH, glutathione; GPx, glutathione peroxidase; HCY, Homocystein; HGF, Human growth factor; HFD, high-fat diet; HUVECs, human umbilical vein endothelial cells; HAVSMCs, human aortic vascular smooth muscle cells; IL-1β, Interleukin 1 β; I/R, Ischemia/Reperfusion; IS, indoxyl sulfate; ISO, isoproterenol; LVEDD, left ventricular end-diastolic diameter; MI, Myocardial infarction; MDA, malondialdehyde; NF-kB, Nuclear factor kappa-B; ROS, reactive oxygen species; Runx2, Runt-related transcription factor 2; SIRT1, Silent information regulator 1; Sema4b, semaphorin 4B; SOD, superoxide dismutase; TGF-β, Transforming growth factor β; VCAM1, vascular cell adhesion molecule 1; VEGF, Vascular endothelial growth factor.

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