2. Academic Validation
  3. Nicorandil protects against coronary microembolization-induced myocardial injury by suppressing cardiomyocyte pyroptosis via the AMPK/TXNIP/NLRP3 signaling pathway

Nicorandil protects against coronary microembolization-induced myocardial injury by suppressing cardiomyocyte pyroptosis via the AMPK/TXNIP/NLRP3 signaling pathway

  • Eur J Pharmacol. 2022 Nov 3;175365. doi: 10.1016/j.ejphar.2022.175365.
Yangchun Liu 1,  Jin Shu 2,  Tao Liu 2,  Jian Xie 2,  Tao Li 2,  Haoliang Li 2,  Lang Li 3
Affiliations

Affiliations

  • 1 Cardiothoracic Surgery Intensive Care Unit, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: drlilang1968@126.com.
PMID: 36336011 DOI: 10.1016/j.ejphar.2022.175365
Abstract

Background: Coronary microembolization (CME) is a common and intractable complication of coronary revascularization, which leads to perioperative myocardial injury, cardiac dysfunction, and poor prognosis. Nicorandil is widely used for the management of ischemic heart diseases, but the cardioprotective effects of nicorandil beyond anti-angina in CME-induced myocardial injury are worthy of further exploration. Therefore, the present study investigated the effect of nicorandil on CME-induced cardiomyocyte Pyroptosis and explored the underlying mechanism.

Methods: A rat model of CME was established via the injection of microspheres into the left ventricle. A cell model of H9c2 cardiomyocytes stimulated by lipopolysaccharide (LPS) and hypoxia mimicked the microenvironment induced by CME. Nicorandil or the adenosine monophosphate-activated protein kinase (AMPK)-specific inhibitor compound C (CC) was administered before CME induction and cell modeling. Cardiac function, histological alterations in the myocardium, myocardial injury biomarkers in serum and Cell Culture supernatant, cell viability, adenosine triphosphate (ATP) level, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, Reactive Oxygen Species (ROS) activity, mitochondrial membrane potential, and pyroptosis-associated index were assessed after the animal and cell modeling of CME.

Results: Nicorandil pretreatment attenuated cardiac dysfunction and myocardial injury following CME. Nicorandil also alleviated oxidative stress and mitochondrial damage. Moreover, nicorandil promoted AMPK activation, reduced the expression of thioredoxin-interacting protein (TXNIP), inhibited the activation of the NOD-like Receptor pyrin containing 3 (NLRP3) inflammasome, and mitigated cardiomyocyte Pyroptosis. However, co-treatment with CC reversed the cardioprotective effects of nicorandil.

Conclusion: Nicorandil pretreatment inhibits cardiomyocyte Pyroptosis and alleviates CME-induced myocardial injury via the AMPK/TXNIP/NLRP3 signaling pathway.

Keywords

AMPK/TXNIP/NLRP3; Cardiomyocyte; Coronary microembolization; Myocardial injury; Nicorandil; Pyroptosis.

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