Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia.

ABSTRACT: Iron homeostasis is crucial for optimal cardiac function. Iron deficiency and overload have been linked to the development of cardiomyopathy and heart failure (HF) via intricate mechanisms. Although the crucial role of SLC40A1 in iron metabolism by facilitating the efflux of cellular iron has been confirmed, its specific molecular functions in cardiovascular diseases remain poorly understood. In this study, we generated mice with inducible cardiomyocyte-specific overexpression of SLC40A1 for the first time. The overexpression of SLC40A1 in the cardiomyocytes of adult mice resulted in significant iron deficiency, leading to mitochondrial dysfunction, oxidative stress, and apoptosis, subsequently resulting in the development of fatal HF. Notably, SLC40A1 upregulation was observed in the isch

SUBMITTER: Feng R 

PROVIDER: S-EPMC10758104 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature