Integrin αv contributes to the regulation of vascular smooth muscle cell stiffness.

Arterial stiffening is influenced by the organization of focal adhesions in vascular smooth muscle cells (VSMCs). We investigated the contribution of αv integrins to both arterial wall stiffness (Young's modulus measured by echography) and VSMC stiffness (assessed by atomic force microscopy). Mice with VSMC-specific deletion of αv integrins (αvSMKO) were compared with controls at baseline and following angiotensin II infusion. Unstimulated cultured αv-deficient (αv-KD) VSMCs exhibited higher stiffness than controls, with a further increase after angiotensin II. To interpret AFM measurements performed at shallow indentation depths, we developed a computational model of VSMC nanoindentation. Simulations showed that higher apparent Young's moduli at shallow indentation fall within the experimental range of αv-KD cells. These cells also displayed enhanced actin polymerization, further amplified by angiotensin II through the formation of cortical F-actin. In vivo, arterial pressure and wall elastic modulus were similar between αvSMKO and control mice at baseline and after angiotensin II, despite αvSMKO mice exhibiting lower elastin and higher collagen content under angiotensin II. Together, these findings indicate that the comparable increase in arterial stiffness observed in αvSMKO mice under angiotensin II is driven primarily by elevated VSMC stiffness resulting from cortical actin redistribution, which outweighs extracellular matrix changes.