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MicroRNA-221/222 regulate ox-LDL-induced endothelial apoptosis via Ets-1/p21 inhibition

Mol Cell Biochem. 2015 Jul;405(1-2):115-24. doi: 10.1007/s11010-015-2403-5. Epub 2015 Apr 17.

Abstract

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play an essential role in atherosclerosis. MicroRNAs (miRNAs) are a class of short non-coding RNAs, acting as posttranscriptional regulators of protein-coding genes involved in vascular cell biology. MiRNA-221 and miRNA-222 (miR-221/222) are known to be involved in the regulation of endothelial inflammation and angiogenesis. However, the function of miR-221/222 in ox-LDL-induced ECs apoptosis and atherosclerosis is still unknown. Here, we showed that miR-221/222 expression was markedly down-regulated in ox-LDL-induced apoptotic human umbilical cord vein endothelial cells. MiR-221/222 inhibition enhanced apoptosis in ECs, whereas over-expression of miR-221/222 could partly alleviate apoptotic cell death mediated by ox-LDL through suppression of Ets-1 and its downstream target p21. These findings suggest that manipulation of the miR-221/222-Ets-1-p21 pathway may offer a novel strategy for treatment of endothelial apoptosis and atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Down-Regulation / genetics
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Gene Expression Regulation / genetics
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / adverse effects*
  • MicroRNAs / genetics*
  • Proto-Oncogene Protein c-ets-1 / antagonists & inhibitors*
  • Proto-Oncogene Protein c-ets-1 / genetics

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • ETS1 protein, human
  • Lipoproteins, LDL
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Protein c-ets-1
  • oxidized low density lipoprotein