2. Academic Validation
  3. Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway

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

  • Biomed Pharmacother. 2020 Jul:127:110121. doi: 10.1016/j.biopha.2020.110121.
Biming Zhan 1,  Zongyu Xu 2,  Yang Zhang 3,  Kefei Wan 4,  Hanyue Deng 4,  Dimeng Wang 4,  Huihui Bao 1,  Qinghua Wu 1,  Xiaohong Hu 1,  Hong Wang 5,  Xiao Huang 6,  Xiaoshu Cheng 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China.
  • 2 Department of Cardiology, Huangpu Branch of the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University, China.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, China.
  • 4 Clinical Medicine, Medical College of Nanchang University, China.
  • 5 Center for Metabolic Disease Research, Department of Pharmacology Lewis Katz School of Medicine, Temple University, 3500 Broad Street, Philadelphia, PA, 19140, United States.
  • 6 Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. Electronic address: [email protected].
  • 7 Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, China. Electronic address: [email protected].
PMID: 32407984 DOI: 10.1016/j.biopha.2020.110121
Abstract

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.

Keywords

Coronary microvascular dysfunction; Homocysteine; Nicorandil; PI3K/Akt/eNOS pathway.

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