Model.

(A) Tension-induced, Src- and FAK-mediated growth and remodeling of dynamic focal adhesions in aortic VSMCs leads to cell-matrix adhesion strengthening (cortical stiffening) in response to contractile stimulus. This strengthening is required for adequate force and stiffness transmission from the VSMC to the blood vessel wall. (B) Inhibition of Src with PP2 or FAK with FI-14 inhibits FA dynamics and growth, preventing reinforcement of the cell-matrix linkage. As a result, forces and stiffness generated by the activated VSMC cannot propagate efficiently to the tissue. (C) Inhibition of MLCK with ML-9 reduces contractile force and, as a result, lessens reinforcement of the cell-matrix linkage. Consequently, force and stiffness development in the aortic wall are reduced.