2. Academic Validation
  3. BCAA exaggerated acute and chronic ischemic heart disease through promotion of NLRP3 via Sirt1

BCAA exaggerated acute and chronic ischemic heart disease through promotion of NLRP3 via Sirt1

  • Biochem Pharmacol. 2025 Jul 12:241:117150. doi: 10.1016/j.bcp.2025.117150.
Yajie Peng 1,  Yusen Duan 1,  Diya Wang 1,  Jingjing Liu 1,  Guangyuan Zhao 1,  Zhangyue Ji 1,  Ji Zhang 2,  Bo Wei 3
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
  • 2 Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China. Electronic address: fcczhangj@zzu.edu.cn.
  • 3 Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China. Electronic address: weibo@zzu.edu.cn.
PMID: 40659126 DOI: 10.1016/j.bcp.2025.117150
Abstract

The study investigated the role and mechanism of branched chain amino acid (BCAA) metabolism in acute myocardial injury and ventricular remodeling post-myocardial infarction. This research employed an integrated approach, combining Molecular Biology with metabolomics, to investigate the influence of BCAA on acute and chronic myocardial injury both in vivo and in vitro, respectively. In acute myocardial injury, BCAA significantly aggravated acute myocardial injury as demonstrated by remarkably worsen cardiac function and exacerbated biochemical abnormalities, and increased infarct size. Furthermore, BCAA supplementation aggravated the defective metabolism of BCAA by inhibiting the activities of BCAT2, BCKDH and PP2Cm. Interestingly, BCAA dose-dependently promoted Pyroptosis in cardiomyocytes via NLRP3/ASC/Caspase-1 activation and cleaved GSDMD in acute myocardial injury. On the Other hand, in long-term myocardial infarction (L-MI) induced remodeling, BCAA aggravated the ventricular remodeling in L-MI, and exacerbated the impairment in BCAA metabolism by inhibiting the activities of BCAT2, BCKDH, and PP2Cm. Interestingly, BCAA promoted inflammation in cardiac fibroblasts (CF) in dose-dependently. This process was mediated by inhibiting SIRT1 and enhancing NLRP3 acetylation, thereby activating the NLRP3 inflammasome and promoting CF migration, but without the trigger of Pyroptosis. While Knockdown of SIRT1 markedly inhibited NLRP3 activation induced by BCAA in CF. In summary, this study provided a theoretical foundation for developing novel strategies to prevent and treat cardiovascular diseases, and offered valuable guidance for the dietary management of patients with myocardial injury.

Keywords

Acute myocardial infarction; Branched chain amino acids; Myocardial ischemia/reperfusion; NLRP3; Sirt1; Ventricular remodeling.

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