Cytochrome P450 2E1 aggravates DXR-induced myocardial injury through imbalanced mitochondrial OPA1.

ABSTRACT:

Background

Cytochrome P450 2E1 (CYP2E1), a drug metabolism enzyme, is linked to multiple pathophysiological states in the myocardium and may act as a sensor of heart diseases. However, the exact mechanisms of CYP2E1 in myocardial injury, particularly in chemotherapeutic agent-induced myocardial damage such as doxorubicin-induced cardiotoxicity, remain unclear.

Methods

Using multiple animal models of cardiomyopathy and heart failure, we observed CYP2E1 expression in myocardial mitochondria. Myocardium-specific CYP2E1 overexpression and knockout rat models were employed to study its effects on myocardial injury, assessed via echocardiography and histopathology. Mechanistic insights were derived from transcriptome analysis, mass spectrometry, co-immunoprecipitation, signal tran

SUBMITTER: Ma J 

PROVIDER: S-EPMC12042624 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature