MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis

Sci Rep. 2015 Mar 24;5:9401. doi: 10.1038/srep09401.

Abstract

Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE(-/-) mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apoptosis / drug effects
  • Atherosclerosis / etiology
  • Atherosclerosis / genetics*
  • Atherosclerosis / pathology
  • Base Sequence
  • Calcium Signaling*
  • Cell Line
  • Cell Survival / drug effects
  • Diet, High-Fat / adverse effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Lipoproteins, LDL / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • TRPC Cation Channels / genetics*
  • TRPC Cation Channels / metabolism
  • Tunica Intima / drug effects
  • Tunica Intima / metabolism
  • Tunica Intima / pathology

Substances

  • Apolipoproteins E
  • Lipoproteins, LDL
  • MicroRNAs
  • Mirn26 microRNA, mouse
  • TRPC Cation Channels
  • Trpc6 protein, mouse
  • oxidized low density lipoprotein
  • Luciferases