PMID- 34144026 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 907 DP - 2021 Sep 15 TI - Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition. PG - 174260 LID - S0014-2999(21)00413-1 [pii] LID - 10.1016/j.ejphar.2021.174260 [doi] AB - Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague-Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 mug/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Yang, Li-Guo AU - Yang LG AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Provincial People's Hospital, Taiyuan, 030001, Shanxi, PR China. FAU - Wang, Ai-Ling AU - Wang AL AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Li, Lu AU - Li L AD - Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Yang, Hong AU - Yang H AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Jie, Xi AU - Jie X AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Zhu, Zong-Feng AU - Zhu ZF AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Zhang, Xiao-Juan AU - Zhang XJ AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Province Cardiovascular Hospital, Taiyuan, 030024, Shanxi, PR China. FAU - Zhao, Hui-Ping AU - Zhao HP AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Chi, Rui-Fang AU - Chi RF AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Li, Bao AU - Li B AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Qin, Fu-Zhong AU - Qin FZ AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. Electronic address: sxcvh13@sina.com. FAU - Wang, Jia-Pu AU - Wang JP AD - Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Province Cardiovascular Hospital, Taiyuan, 030024, Shanxi, PR China. FAU - Wang, Ke AU - Wang K AD - The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. LA - eng PT - Journal Article DEP - 20210616 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Lysophospholipids) RN - 26993-30-6 (sphingosine 1-phosphate) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - Animals MH - Autophagy MH - *Lysophospholipids MH - Myocardial Infarction MH - Myocytes, Cardiac MH - Rats MH - Rats, Sprague-Dawley MH - Sphingosine/*analogs & derivatives OTO - NOTNLM OT - Left ventricular remodeling OT - Myocardial infarction OT - Myocyte autophagy OT - Sphingosine-1-phosphate OT - mTOR EDAT- 2021/06/19 06:00 MHDA- 2021/12/24 06:00 CRDT- 2021/06/18 20:11 PHST- 2021/01/14 00:00 [received] PHST- 2021/06/05 00:00 [revised] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/06/19 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/06/18 20:11 [entrez] AID - S0014-2999(21)00413-1 [pii] AID - 10.1016/j.ejphar.2021.174260 [doi] PST - ppublish SO - Eur J Pharmacol. 2021 Sep 15;907:174260. doi: 10.1016/j.ejphar.2021.174260. Epub 2021 Jun 16.