Mechanisms of AGE-induced VSMC phenotypic switching and macrophage modulation in human abdominal aortic aneurysms.

ABSTRACT: Advanced glycation end products (AGEs) have been associated with vascular pathologies including abdominal aortic aneurysms (AAAs), although their causal role remains unclear. In this study, we observed significant accumulation of AGEs in human AAAs, particularly in cases associated with intraluminal thrombus (ILT). In vitro, AGE exposure induced vascular smooth muscle cell (VSMC) migration and suppressed contractility, accompanied by reduced expression of contractile markers (α-SMA and MYH11) and elevated MMP-2. This phenotypic transformation was linked to the activation of the NLRP3 inflammasome and RAGE/RhoA/ROCK signaling, and was reversible upon inhibition of RAGE, RhoA, or ROCK. In macrophages, AGE pretreatment had minimal effects on basal cytokine secretion but attenuated LPS-induced

SUBMITTER: Ma X 

PROVIDER: S-EPMC12367564 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature