title: MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis.
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.
authors: 1] Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China [2] Institute of Cardiovascular Research, Harbin Medical University, Harbin 150081, China.
authors: Yong
authors: Y
authors: Zhang
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Wei
authors: W
authors: Qin
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Longyin
authors: L
authors: Zhang
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Xianxian
authors: X
authors: Wu
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Ning
authors: N
authors: Du
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Yingying
authors: Y
authors: Hu
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Xiaoguang
authors: X
authors: Li
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Nannan
authors: N
authors: Shen
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Dan
authors: D
authors: Xiao
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Haiying
authors: H
authors: Zhang
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Zhange
authors: Z
authors: Li
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Yue
authors: Y
authors: Zhang
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Huan
authors: H
authors: Yang
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors: Feng
authors: F
authors: Gao
authors: Institute of Clinical Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors: Zhimin
authors: Z
authors: Du
authors: 1] Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China [2] Institute of Cardiovascular Research, Harbin Medical University, Harbin 150081, China.
authors: Chaoqian
authors: C
authors: Xu
authors: 1] Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China [2] Institute of Cardiovascular Research, Harbin Medical University, Harbin 150081, China.
authors: Baofeng
authors: B
authors: Yang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D020013:Calcium Signaling; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism; D000074287:TRPC6 Cation Channel; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C099252:oxidized low density lipoprotein; D008156:Luciferases