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

Abstract

ObjectiveNicorandil 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. MethodsC57/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. ResultsThe 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. ConclusionThe results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.