Hyperglycemia-induced DNA damage response activates DNA-PK complex to promote endothelial ferroptosis in type 2 diabetic cardiomyopathy.

ABSTRACT: Rationale: Hyperglycemia-induced endothelial dysfunction is a hallmark of diabetic cardiomyopathy, yet the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate how the DNA damage response (DDR) pathway regulates endothelial cell ferroptosis under hyperglycemic conditions, potentially revealing new therapeutic targets for mitigating cardiac damage in type 2 diabetes mellitus (T2DM). Methods: We performed an integrated analysis of publicly available RNA sequencing datasets (GSE280770, GSE89475, GSE161931, CRA007245) to evaluate the role of DDR in hyperglycemia-induced endothelial dysfunction in vitro and in vivo, including in a T2DM mouse model. Key DDR and ferroptosis markers were validated in cardiac microvascular endot

SUBMITTER: Luo C 

PROVIDER: S-EPMC11984385 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature