Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway

Autor: Dimeng Wang, Huihui Bao, Yang Zhang, Xiaoshu Cheng, Kefei Wan, Hanyue Deng, Qinghua Wu, Zongyu Xu, Xiaohong Hu, Biming Zhan, Hong Wang, Xiao Huang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Homocysteine
Myocardial Infarction
Pharmacology
Ventricular Function
Left
Mice
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
0302 clinical medicine
Enos
Coronary microvascular dysfunction
Myocardial infarction
Hypoxia
Nicorandil
Cells
Cultured
Tube formation
biology
General Medicine
PI3K/Akt/eNOS pathway
Platelet Endothelial Cell Adhesion Molecule-1
Nitric oxide synthase
NG-Nitroarginine Methyl Ester
030220 oncology & carcinogenesis
cardiovascular system
Plant Lectins
medicine.drug
Nitric Oxide Synthase Type III
Cell Survival
Morpholines
Hyperhomocysteinemia
RM1-950
03 medical and health sciences
medicine
Animals
Humans
Protein kinase B
PI3K/AKT/mTOR pathway
business.industry
Microcirculation
Endothelial Cells
medicine.disease
biology.organism_classification
030104 developmental biology
chemistry
Chromones
biology.protein
Therapeutics. Pharmacology
business
Proto-Oncogene Proteins c-akt
Zdroj: Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110121-(2020)
ISSN: 0753-3322
Popis: 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.
Databáze: OpenAIRE
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