Understanding the functional role of microRNA‐214‐3p in atherosclerosis for the identification of novel targeted therapies to prevent or reverse endothelial cell dysfunction and stimulate autophagy

Abstract

L. 2017. MicroRNA-214-3p: a link between autophagy and endothelial cell dysfunction in atherosclerosis. Acta Physiol 222, e12973.The original article by Wang et al., entitled "MicroRNA-214-3p: A Link between Autophagy and Endothelial Cell Dysfunction in Atherosclerosis," brings new data concerning molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis. In this issue of Acta Physiologica, the authors concluded that microRNA-214-3p (miR-214-3p) controls oxidized low-density lipoprotein (ox-LDL)-induced autophagy in human umbilical vein endothelial cells (HUVECs) by regulating intracellular levels of autophagy-related protein 5 (ATG5) and may have a relevant role in the pathogenesis of atherosclerosis.This study was carried out through in vivo and in vitro experiments conducted in ApoE À/À mice supplied with highfat diet (HFD) as atherosclerosis model and HUVECs. In vivo experiments, ATG5, ATG12 and miR-214-3p levels were analysed in the purified CD31 + endothelial cells from mouse aorta. Interesting, prediction of the binding between miR-214-3p and 3 0 -UTR of ATG5 mRNA was performed by bioinformatics analyses. In vitro experiments, HUVECs were transfected in order to modulate miR-214-3p and stimulated with ox-LDL to induce a stress-repairing autophagic process. The authors showed in their experimental study three very important aspects: (i) in atherosclerotic mouse model, they identified an inverse correlation between miR-214-3p and ATG5 and ATG12; (ii) in young HUVEC, they found ox-LDL-induced autophagy as evidenced by the increases in ATG5, ATG12 and microtubule-associated protein 1 light chain 3 (LC3B) protein levels with a simultaneously decreased SQSTM1/p62 protein level, and miR-214-3p overexpression reduced autophagy; (iii) in old HUVECs, inhibition of the miR-214-3p increased their protective autophagy response to the ox-LDL stimulus, as evaluated by autophagic protein analysis, LC3B immunofluorescence assay and transmission electron microscopy (TEM). 1The microRNAs (miRNAs), small non-coding RNA molecules, are posttranscriptional regulators of gene expression by their action on target mRNAs controlling their translation and degradation, modulating in this way various cellular and developmental processes.2 They have a substantial contribution to cardiovascular physiology and pathology, and their abnormal expression has been associated with atherosclerosis and cardiovascular diseases, they being involved in the putative mechanisms that lead to endothelial dysfunction and vascular damage. Recently, autophagy or type II programmed cell death has been considered to be involved in the regulation of cell death and survival, as well as in the progression of atherosclerosis, whereas acquired defects in plaque autophagy exacerbate atherosclerosis. 4 However, the underlying molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis have not been fully explored.To date, several miRNAs involved in endothelial dysfunction through autophagy de...

LncRNA Miat knockdown alleviates endothelial cell injury through regulation of miR‐214‐3p/Caspase‐1 signalling during atherogenesis

“…The miR‐214 level was significantly lower in coronary artery disease patients compared with that in controls, which may be a biomarker for alerting severe coronary artery disease 24 . Also, miR‐214‐3p was downregulated in HAECs stimulated with ox‐LDL 25,26 …”

Listen to your physiologist!

“…Wang et al recently observed a novel link between decreased stress‐related autophagy and endothelial dysfunction in atherosclerosis, mediated by miR‐214‐3p …”

microRNA‐107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1‐dependent Notch signaling pathway in a mouse model of coronary atherosclerosis

“…Therefore, a thorough understanding of the potential pathophysiological mechanisms involving the above factors is of great importance for the development of novel therapeutic strategies in atherosclerosis (Brown et al, 2016). Recently, microRNA (miRNA)targeted therapies are proposed to limit the morphology of atherosclerotic plaque and reverse the dysfunction of endothelial cells, thus, to prevent the progression of atherosclerosis (Georgescu, 2018;Lovren et al, 2012).…”