Pharmacological targeting of plasminogen activator inhibitor-1 decreases vascular smooth muscle cell stiffness and cytoskeletal F-actin stress fiber density

Abstract

Vascular stiffness plays a key role in cardiovascular diseases, and recent studies suggest that intrinsic stiffness of vascular smooth muscle cells (SMCs) accounts for as much as one-half of overall arterial stiffness. SMCs express plasminogen activator inhibitor-1 (PAI-1), a key regulator of proteolysis that regulates SMC function and vascular remodeling through effects on pericellular proteolysis and integrinmatrix binding interactions. The objective of this study is to examine the effects of PAI-1 on other aspects of SMC function, including cell stiffness, and cytoskeletal structure. Given that PAI-1 inhibitors represent an emergent potential therapy for cardiovascular and other disorders, we hypothesized that PAI-1 inhibition decreases SMCs stiffness.