Leucine aggravated acute myocardial injury induced by myocardial infarction via promotion of NLRP3 signaling pathway
- VernacularTitle:亮氨酸通过促进NLRP3炎症通路激活加重急性心肌梗死致心肌损伤
- Author:
Shuai ZHOU
1
;
Ya-jie PENG
;
Lu-lu LYU
;
Bo WEI
Author Information
- Publication Type:Journal Article
- Keywords: acute myocardial infarction; branched chain amino acid; leucine; NLRP3; inflammation; my-ocardial infarction
- From: Chinese Pharmacological Bulletin 2025;41(10):1922-1931
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the exact branched-chain amino acid(BCAA)that exacerbates acute myocardial infarction(MI)injury and mechanisms of such action.Methods At the cellular level,myocardial injury model was stimulated in H9c2 cells subjected to H2O2.The effects of the three branched-chain amino acids on MI were evaluated by measuring MTT,LDH leakage rate and cellular morphology.In vivo,the MI model was established by ligating the coronary left anterior descending artery.Electrocardiography,echocardio-graphy,TTC staining and histopathological detection were conducted.Additionally,Western blot was used to determine the effect of leucine on inflammatory sig-naling pathway in vitro.Results At the cellular lev-el,BCAA pretreatment could further inhibit the surviv-al rate of cardiomyocytes,increase LDH leakage rate,markedly decrease cell numbers and obviously shrink-age morphology,thus aggravating acute injury in car-diomyocytes.In vivo,leucine or BCAA pretreatment further deteriorated the cardiac function,increased the cardiac infarct size,worsened the histopathological changes,increased levels of the serum CK-MB and AST in the MI group rats,and ultimately exacerbated the MI injury in rats.Additionally,leucine could dosedependently exacerbate the activation of the NL-RP3 inflammasome signaling pathway induced by H2O2 stimulation in H9c2 cells.Conclusion The exacerba-ting effect of BCAA on MI injury is mainly exerted through leucine,and this effect is associated with the activation of the NLRP3 inflammasome.
