Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
LuQi formula mitigates ventricular remodeling in myocardial infarction via SPTLC2-regulated de novo ceramide synthesis.
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Guo Jiaying, Liu Mengfan, Xi Zhichao, Yan Jirong, Zhang Yibo, Hu Jingqi, Zhang Jinying, Xu Hongxi, Zhou Hua
Аннотация
BACKGROUND: Ventricular remodeling is a compensatory response to myocardial infarction (MI), leading to an elevated risk of heart failure. Ceramide accumulation within cardiac tissue plays a critical role in the development of ventricular remodeling, mediating the detrimental effects of cardiac lipotoxicity. LuQi Formula (LQF), an herbal preparation in traditional Chinese medicine, has gained extensive application in clinical treatment to improve cardiac function in heart failure patients. However, the underlying mechanisms warrant in-depth investigation.
PURPOSE: This study aims to explore whether LQF attenuates post-MI remodeling by regulating ceramide synthesis and to elucidate the underlying mechanisms.
METHODS: An acute MI model was established in rats through permanently ligating the left anterior descending coronary artery. Echocardiography and tissue histopathology were assessed to evaluate cardiac function. To model lipotoxicity-induced myocardial injury, palmitate was used to increase ceramide levels in H9C2 cardiomyocytes. Ceramide expression was evaluated by immunofluorescence, western blotting, and RT‒qPCR. Cardiomyocyte apoptosis was examined by TUNEL staining and Annexin V-FITC/PI flow cytometry. SiRNA transfection and modRNA overexpression were employed to elucidate the mechanism by which LQF alleviates myocardial injury.
RESULTS: LQF significantly alleviated ventricular remodeling and improved acute MI-induced cardiac function in the rat model. LQF reduced ceramide accumulation and inhibited cardiomyocyte apoptosis post-MI induction both in vitro and in vivo. Mechanistically, LQF downregulates the expression of serine palmitoyltransferase long chain base subunit 2 (SPTLC2), thereby suppressing de novo ceramide synthesis. Decreasing SPTLC2 reduced cardiomyocyte apoptosis, with LQF treatment further enhancing these anti-apoptotic effects in SPTLC2-knockdown H9C2 cells. Moreover, SPTLC2 overexpression reversed these effects, restoring ceramide levels and diminishing LQF's cardioprotective benefits.
CONCLUSION: LQF mitigates ventricular remodeling, reduces ceramide accumulation by downregulating SPTLC2, and inhibits MI-induced cardiomyocyte apoptosis. These findings underscore LQF's unique regulation of sphingolipid metabolism, highlight its therapeutic potential, and indicate SPTLC2-mediated ceramide signaling as a novel target for ameliorating post-MI remodeling.
PURPOSE: This study aims to explore whether LQF attenuates post-MI remodeling by regulating ceramide synthesis and to elucidate the underlying mechanisms.
METHODS: An acute MI model was established in rats through permanently ligating the left anterior descending coronary artery. Echocardiography and tissue histopathology were assessed to evaluate cardiac function. To model lipotoxicity-induced myocardial injury, palmitate was used to increase ceramide levels in H9C2 cardiomyocytes. Ceramide expression was evaluated by immunofluorescence, western blotting, and RT‒qPCR. Cardiomyocyte apoptosis was examined by TUNEL staining and Annexin V-FITC/PI flow cytometry. SiRNA transfection and modRNA overexpression were employed to elucidate the mechanism by which LQF alleviates myocardial injury.
RESULTS: LQF significantly alleviated ventricular remodeling and improved acute MI-induced cardiac function in the rat model. LQF reduced ceramide accumulation and inhibited cardiomyocyte apoptosis post-MI induction both in vitro and in vivo. Mechanistically, LQF downregulates the expression of serine palmitoyltransferase long chain base subunit 2 (SPTLC2), thereby suppressing de novo ceramide synthesis. Decreasing SPTLC2 reduced cardiomyocyte apoptosis, with LQF treatment further enhancing these anti-apoptotic effects in SPTLC2-knockdown H9C2 cells. Moreover, SPTLC2 overexpression reversed these effects, restoring ceramide levels and diminishing LQF's cardioprotective benefits.
CONCLUSION: LQF mitigates ventricular remodeling, reduces ceramide accumulation by downregulating SPTLC2, and inhibits MI-induced cardiomyocyte apoptosis. These findings underscore LQF's unique regulation of sphingolipid metabolism, highlight its therapeutic potential, and indicate SPTLC2-mediated ceramide signaling as a novel target for ameliorating post-MI remodeling.