Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching.

ABSTRACT: Vascular smooth muscle cells (VSMCs) play a central role in the progression of atherosclerosis, where they switch from a contractile to a synthetic phenotype. Because of their role as risk factors for atherosclerosis, we sought here to systematically study the impact of matrix stiffness and (hemodynamic) pressure on VSMCs. Thereby, we find that pressure and stiffness individually affect the VSMC phenotype. However, only the combination of hypertensive pressure and matrix compliance, and as such mechanical stimuli that are prevalent during atherosclerosis, leads to a full phenotypic switch including the formation of matrix-degrading podosomes. We further analyze the molecular mechanism in stiffness and pressure sensing and identify a regulation through different but overlapping pathways cul

SUBMITTER: Swiatlowska P 

PROVIDER: S-EPMC9012473 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature