Integrin α_v 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 α_v 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 α_v integrins (α_v^SMKO) were compared with controls at baseline and following angiotensin II infusion. Unstimulated cultured α_v-deficient (α_v-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 α_v-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 α_v^SMKO and control mice at baseline and after angiotensin II, despite α_v^SMKO mice exhibiting lower elastin and higher collagen content under angiotensin II. Together, these findings indicate that the comparable increase in arterial stiffness observed in α_v^SMKO mice under angiotensin II is driven primarily by elevated VSMC stiffness resulting from cortical actin redistribution, which outweighs extracellular matrix changes.