title: Upregulation of miR-142-5p in atherosclerotic plaques and regulation of oxidized low-density lipoprotein-induced apoptosis in macrophages.
abstract: MicroRNA (miR)‑142‑5p is a member of the miR‑142 family, which have been shown to be associated with tumors, stem cells and disorders of the immune system. However, the role of miR‑142‑5p in atherosclerosis has yet to be investigated. In the present study, an atherosclerotic apolipoprotein E‑deficient (apoE‑/‑) mouse model was constructed and fed a high‑fat diet. The expression levels of miR‑142‑5p in the murine atherosclerotic plaques were detected by gene microarray analysis. In addition, an in vitro assay was used to determine the expression levels of miR‑142‑5p in human endothelial cells, smooth muscle cells and macrophages, which were treated with oxidized low‑density lipoprotein (ox‑LDL). Furthermore, a miR‑142‑5p inhibitor and mimic was transfected into cultured human macrophages, in order to observe the effects on transforming growth factor‑β2 (TGF‑β2) expression. The effects of co‑transfection of the miR‑142‑5p inhibitor or mimic with TGF‑β2, in human macrophages, on the rate of apoptosis was analyzed. The expression levels of miR‑142‑5p were 6.84‑fold higher in mice with stable atherosclerotic plaques, and 2.69‑fold higher in mice with vulnerable atherosclerotic plaques, as compared with the controls. Furthermore, the expression levels of miR‑142‑5p were upregulated in the cultured human macrophages. The percentage of apoptotic cells was lowest in the macrophages transfected with both TGF‑β2 and miR‑142‑5p inhibitors and treated with ox‑LDL. The expression levels of miR‑142‑5p were upregulated in the atherosclerotic plaques of the apoE‑/‑ mice. The findings of the present study have shown that the upregulation of miR‑142‑5p expression may regulate apoptosis in human macrophages by targeting TGF‑β2. This effect may have an important role in the progression of atherosclerosis.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Bi
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Song
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ge
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Chinese Ministries of Education and Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D017209:Apoptosis / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004847:Epithelial Cells; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D053781:Transforming Growth Factor beta2; C099252:oxidized low density lipoprotein