title: MicroRNA-221/222 regulate ox-LDL-induced endothelial apoptosis via Ets-1/p21 inhibition.
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.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qin
authors.forename: Yuze
authors.initials: Y
authors.lastname: Cao
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D035683:MicroRNAs / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; C493956:CDKN1A protein, human; C494041:ETS1 protein, human; C525709:MIR221, human; C525710:MIR222, human; C099252:oxidized low density lipoprotein