PINK1 modulates Prdx2 to reduce lipotoxicity‐induced apoptosis and attenuate cardiac dysfunction in heart failure mice with a preserved ejection fraction DOI Creative Commons
Hao Zhang, Tianyu Xu,

Xiyuan Mei

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is a complex condition characterized by metabolic dysfunction and myocardial lipotoxicity. The roles of PTEN‐induced kinase 1 (PINK1) peroxiredoxin‐2 (Prdx2) in HFpEF pathogenesis remain unclear. Objective This study aimed to investigate the interaction between PINK1 Prdx2 mitigate cardiac diastolic HFpEF. Methods In vivo, PINK1‐knockout mice cardiac‐specific PINK1‐overexpressing transgenic were used establish an mouse model via high‐fat diet L‐NAME. Myocardial lipotoxicity was induced palmitic acid vitro. Immunoprecipitation, western blotting immunofluorescence analysis performed elucidate molecular mechanisms involved. Results We determined that downregulated model. ablation exacerbated reduction expression, worsening mice. Conversely, overexpression restored levels decreased reactive oxygen species apoptosis, thereby reducing fibrosis inflammation ameliorating vitro, N‐terminal region (amino acids 1–133) identified. expression effectively attenuated acid‐induced apoptosis through c‐Jun amino‐terminal (JNK) mitogen‐activated protein (p38) pathways, whereas siRNA‐mediated knockdown abolished protective effect PINK1. Conclusion alleviates lipotoxicity‐induced improves Prdx2, highlighting as potential therapeutic strategy for Key points Our investigation discloses pivotal relationship context Notably, PINK1, addition its role mitochondrial autophagy, can increase remove ROS attenuate cardiomyocyte modulating JNK p38 alleviating improving function. studies offer valuable insights, opening avenues development innovative strategies prevention treatment

Язык: Английский

PINK1 modulates Prdx2 to reduce lipotoxicity‐induced apoptosis and attenuate cardiac dysfunction in heart failure mice with a preserved ejection fraction DOI Creative Commons
Hao Zhang, Tianyu Xu,

Xiyuan Mei

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is a complex condition characterized by metabolic dysfunction and myocardial lipotoxicity. The roles of PTEN‐induced kinase 1 (PINK1) peroxiredoxin‐2 (Prdx2) in HFpEF pathogenesis remain unclear. Objective This study aimed to investigate the interaction between PINK1 Prdx2 mitigate cardiac diastolic HFpEF. Methods In vivo, PINK1‐knockout mice cardiac‐specific PINK1‐overexpressing transgenic were used establish an mouse model via high‐fat diet L‐NAME. Myocardial lipotoxicity was induced palmitic acid vitro. Immunoprecipitation, western blotting immunofluorescence analysis performed elucidate molecular mechanisms involved. Results We determined that downregulated model. ablation exacerbated reduction expression, worsening mice. Conversely, overexpression restored levels decreased reactive oxygen species apoptosis, thereby reducing fibrosis inflammation ameliorating vitro, N‐terminal region (amino acids 1–133) identified. expression effectively attenuated acid‐induced apoptosis through c‐Jun amino‐terminal (JNK) mitogen‐activated protein (p38) pathways, whereas siRNA‐mediated knockdown abolished protective effect PINK1. Conclusion alleviates lipotoxicity‐induced improves Prdx2, highlighting as potential therapeutic strategy for Key points Our investigation discloses pivotal relationship context Notably, PINK1, addition its role mitochondrial autophagy, can increase remove ROS attenuate cardiomyocyte modulating JNK p38 alleviating improving function. studies offer valuable insights, opening avenues development innovative strategies prevention treatment

Язык: Английский

Процитировано

1