PMID- 33268288 OWN - NLM STAT- MEDLINE DCOM- 20211221 LR - 20211221 IS - 2452-3186 (Electronic) IS - 2452-3186 (Linking) VI - 69 IP - 1 DP - 2021 Jan TI - Metformin decreased myocardial fibrosis and apoptosis in hyperhomocysteinemia -induced cardiac hypertrophy. PG - 103270 LID - S2452-3186(20)30059-3 [pii] LID - 10.1016/j.retram.2020.103270 [doi] AB - BACKGROUND: Hyperhomocysteinemia (HHcy) is one of the major risk factors of cardiovascular diseases. Metformin acts as a cardioprotective role in several cardiovascular diseases, including ischemia/reperfusion, atherosclerosis, and myocardial infarction. However, whether metformin protects against HHcy-induced cardiac hypertrophy is unclear. METHODS AND RESULTS: HHcy model was established in C57BL/6 mice with high L-methionine (L-MET) diet for 12 weeks. AC16 cells were exposed to homocysteine (Hcy) and then intervened with different concentrations of metformin in in vitro studies. The results showed that HHcy was able to induce cardiac hypertrophy, and metformin could abrogate this effect. HHcy increased the fibrosis area and induced apoptosis in the myocardium, whereas metformin could reverse the detrimental effects above. TUNEL assay showed that metformin was able to decrease Hcy-induced apoptosis in AC16 cells. Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2. CONCLUSIONS: This study demonstrates that metformin is able to attenuate HHcy-induced cardiac hypertrophy by decreasing myocardial fibrosis and apoptosis. CI - Copyright (c) 2020 Elsevier Masson SAS. All rights reserved. FAU - Zhao, Qinshuo AU - Zhao Q AD - Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China. FAU - Song, Wei AU - Song W AD - Department of Pharmacy, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China. FAU - Huang, Jingqiu AU - Huang J AD - Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. FAU - Wang, Dong AU - Wang D AD - Department of Cardiology, Wuhan No.1 Hospital, Huazhong University of Science and Technology, 215 Zhongshan Avenue, Wuhan, 430022, China. FAU - Xu, Changwu AU - Xu C AD - Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China. Electronic address: xuchangwu@whu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201023 PL - France TA - Curr Res Transl Med JT - Current research in translational medicine JID - 101681234 RN - 9100L32L2N (Metformin) SB - IM MH - Adult MH - Animals MH - Apoptosis/*drug effects MH - *Cardiomegaly/drug therapy/etiology/pathology MH - Cells, Cultured MH - Fibrosis MH - Heart/drug effects MH - Humans MH - *Hyperhomocysteinemia/complications/drug therapy/pathology MH - Male MH - Metformin/*pharmacology/therapeutic use MH - Mice MH - Mice, Inbred C57BL MH - Myocardium/*pathology OTO - NOTNLM OT - Apoptosis OT - Cardiac hypertrophy OT - Homocysteine OT - Metformin OT - Myocardial fibrosis EDAT- 2020/12/04 06:00 MHDA- 2021/12/22 06:00 CRDT- 2020/12/03 05:32 PHST- 2020/02/11 00:00 [received] PHST- 2020/08/23 00:00 [revised] PHST- 2020/10/04 00:00 [accepted] PHST- 2020/12/04 06:00 [pubmed] PHST- 2021/12/22 06:00 [medline] PHST- 2020/12/03 05:32 [entrez] AID - S2452-3186(20)30059-3 [pii] AID - 10.1016/j.retram.2020.103270 [doi] PST - ppublish SO - Curr Res Transl Med. 2021 Jan;69(1):103270. doi: 10.1016/j.retram.2020.103270. Epub 2020 Oct 23.