PMID- 32407984 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20210216 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 127 DP - 2020 Jul TI - Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway. PG - 110121 LID - S0753-3322(20)30313-9 [pii] LID - 10.1016/j.biopha.2020.110121 [doi] AB - OBJECTIVE: Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear. METHODS: C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway. RESULTS: The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups. CONCLUSION: The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved. FAU - Zhan, Biming AU - Zhan B AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. FAU - Xu, Zongyu AU - Xu Z AD - Department of Cardiology, Huangpu Branch of the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University, China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, China. FAU - Wan, Kefei AU - Wan K AD - Clinical Medicine, Medical College of Nanchang University, China. FAU - Deng, Hanyue AU - Deng H AD - Clinical Medicine, Medical College of Nanchang University, China. FAU - Wang, Dimeng AU - Wang D AD - Clinical Medicine, Medical College of Nanchang University, China. FAU - Bao, Huihui AU - Bao H AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. FAU - Wu, Qinghua AU - Wu Q AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. FAU - Hu, Xiaohong AU - Hu X AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. FAU - Wang, Hong AU - Wang H AD - Center for Metabolic Disease Research, Department of Pharmacology Lewis Katz School of Medicine, Temple University, 3500 Broad Street, Philadelphia, PA, 19140, United States. FAU - Huang, Xiao AU - Huang X AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. Electronic address: drhuangxiao@163.com. FAU - Cheng, Xiaoshu AU - Cheng X AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. Electronic address: drchengxiaoshu@163.com. LA - eng PT - Journal Article DEP - 20200511 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Chromones) RN - 0 (Morpholines) RN - 0 (Pecam1 protein, mouse) RN - 0 (Plant Lectins) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (tomato lectin) RN - 0LVT1QZ0BA (Homocysteine) RN - 260456HAM0 (Nicorandil) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chromones/pharmacology MH - Endothelial Cells/drug effects MH - Homocysteine MH - Humans MH - Hyperhomocysteinemia/chemically induced/*prevention & control MH - Hypoxia MH - Male MH - Mice MH - Microcirculation/*physiology MH - Morpholines/pharmacology MH - Myocardial Infarction/physiopathology/prevention & control MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Nicorandil/antagonists & inhibitors/*pharmacology MH - Nitric Oxide Synthase Type III/*metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Plant Lectins/biosynthesis MH - Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Ventricular Function, Left/physiology OTO - NOTNLM OT - Coronary microvascular dysfunction OT - Homocysteine OT - Nicorandil OT - PI3K/Akt/eNOS pathway COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2020/05/15 06:00 MHDA- 2021/02/17 06:00 CRDT- 2020/05/15 06:00 PHST- 2019/12/26 00:00 [received] PHST- 2020/03/18 00:00 [revised] PHST- 2020/03/27 00:00 [accepted] PHST- 2020/05/15 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/05/15 06:00 [entrez] AID - S0753-3322(20)30313-9 [pii] AID - 10.1016/j.biopha.2020.110121 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Jul;127:110121. doi: 10.1016/j.biopha.2020.110121. Epub 2020 May 11.