Cell Biol Int. 2026 Oct;50(10):e70212. doi: 10.1002/cbin.70212.
ABSTRACT
Diabetic cardiomyopathy (DCM) induces myocardial lipotoxicity, mitochondria are essential for lipid metabolism. This study explored the role of mitochondria-related gene Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) in DCM. Mitochondria-related differentially expressed genes(Mito DEGs) were screened from DCM and mitochondrial datasets. Protein-protein interaction (PPI) network and CytoHubba were applied to identify hub Mito DEGs. Hub gene expression in vivo and vitro DCM models was verified by western blot and RT-qPCR. H9C2 cell apoptosis was detected by Tunel and flow cytometry, lipid accumulation was clarified by oil red O staining, oxidative stress was assessed by detecting ROS, BODIPY-C11 and malondialdehyde(MDA). Mitochondrial function was determined by JC-1 staining and ATP levels. After adding Fenofibrate(FNB), apoptosis proteins were detected by western blot. DCM genes are enriched in fatty acid metabolism pathway. EHHADH is the most critical hub gene in all hub Mito DEGs and upregulated in vivo and vitro DCM models. EHHADH knockdown aggravate high glucose and palmitic acid (HGHP)-treated H9C2 cell apoptosis, oxidative stress, lipid peroxidation, and lipid accumulation, which are associated with mitochondrial functional damage. FNB promoted EHHADH expression, thereby reducing apoptosis, lipid accumulation, and mitochondrial damage in myocardial cells. EHHADH exerts a protective effect in DCM by reducing mitochondrial damage, oxidative stress, lipid accumulation, and cardiomyocyte apoptosis.
PMID:42765461 | DOI:10.1002/cbin.70212