Mechanical Stress Triggers Premature Senescence in Cardiac Fibroblasts.

ABSTRACT: The cardiovascular system functions under continuous cyclic mechanical stretch, with disruptions in mechanical and biochemical signals contributing to disease progression. In cardiovascular disorders, these disruptions activate cardiac fibroblasts (CFs) and promote cellular senescence, yet it remains unclear whether mechanical stimuli alone can initiate this phenotype. Here, primary murine CFs are exposed to uniaxial stretch, and systematically varied mechanical parameters assessed their role in senescence induction. Loss of stretch magnitude and increase in frequency, mimicking a pathologic hypertrophy and fibrosis, led to a senescence phenotype, identified through cell cycle arrest, decreased lamin B expression, and DNA damage. Mechanically-induced CF senescence depends on p53/p21, where

SUBMITTER: Schneider SE 

PROVIDER: S-EPMC12713081 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature