Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.

ABSTRACT: Aortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4^R/R mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4^R/R aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4^R/R VSMCs by revealing increased SA-β-gal, p21, and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dil

SUBMITTER: Stefens SJM 

PROVIDER: S-EPMC11189919 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature