Vericiguat reduces pyroptosis in rats with coronary microembolization by inhibiting the AMPK/Nrf2/NLRP3 signaling pathway

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Eksavang Khounphinith You Zhou Zeqiang Yi Tao Li Lang Li
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제6호, 755~767쪽, 전체 13쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.11.30

국문 초록

Coronary microembolization (CME) is a prevalent and refractory complication of coronary revascularization, resulting in perioperative myocardial injury, cardiac dysfunction, and unfavorable prognosis. Vericiguat represents a novel therapeutic agent for chronic heart failure; however, further investigation is warranted to explore its potential cardioprotective effects beyond improving cardiac function in CME-induced myocardial injury. Therefore, the objective of this study is to evaluate the impact of vericiguat on pyroptosis in cardiomyocytes induced by CME and elucidate the underlying mechanism. The CME model was created in 40 Sprague-Dawley rats by injecting microspheres into the left ventricle, with the exception of the sham group. Vericiguat or CC (AMPK inhibitor), was given before creating CME models. Four groups were created for the rats: sham, CME, CME+VER, and CME+VER+CC, with random assignment. The CME+VER and CME+VER+CC groups received oral administration of vericiguat for a duration of two weeks before undergoing CME modeling. Echocardiography, myocardial histopathology, and serum markers of myocardial injury were assessed following induction of CME. Pyroptosis-related molecules and the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-like (Nrf2)/NOD-like receptor pyrin containing 3 (NLRP3) pathway were evaluated using qRT-PCR, Western blotting, ELISA, and immunofluorescence. Vericiguat pretreatment attenuated cardiac dysfunction and myocardial injury following CME. Furthermore, vericiguat ameliorates mitochondrial damage, facilitated AMPK activation, upregulated the expression of Nrf2, suppressed the initiation of the NLRP3 inflammasome and alleviated cardiomyocyte pyroptosis levels. However, the cardioprotective effects of vericiguat were reversed when co-treatment with CC. Vericiguat pretreatment reduces cardiomyocyte pyroptosis and myocardial injury after CME by activating the AMPK/Nrf2/NLRP3 pathway.

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INTRODUCTION

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키워드

AMPK/Nrf2/NLRP3 Cardiac dysfunction Coronary microembolization Myocardial pyroptosis Vericiguat