Elevated Dickkopf 3 Promotes Abdominal Aortic Aneurysm Formation via Modulated Phenotype Switch of Vascular Smooth Muscle Cells.

ABSTRACT: Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease with no effective therapeutic intervention. Vascular smooth muscle cell (VSMC) phenotypic switching and elevated matrix metalloproteinase (MMP) levels are key pathogeneses of AAA, although the underlying regulatory mechanisms remain to be fully elucidated. In our study, single-cell RNA-sequencing data analysis demonstrated a substantial elevation in modulated VSMCs in patients with aortic aneurysm, accompanied by Dickkopf 3 (DKK3) up-regulation. Both systemic DKK3 knockout and VSMC-specific DKK3 knockdown led to a marked decrease in both the incidence and mortality of AAA in mice. Reintroduction of DKK3 in Dkk3 ^-/- Apoe ^-/- mice via adeno-associated virus (AAV) exacerbated AAA develo

SUBMITTER: Cao X 

PROVIDER: S-EPMC12423507 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature