The Role of Syndecan‐1 in Arterial Mechanotransduction

Abstract

Hemodynamic forces induced by blood flow are potent regulators of vascular homeostasis and arterial structure. While previous work has focused on the role of integrin receptors in mechanotransduction, little is known about the role of cell surface proteoglycans in these processes. This work focuses specifically on the role of the cell surface heparan sulfate proteoglycan syndecan‐1 in vascular cell mechanotransduction. We isolated vascular smooth muscle cells from syndecan‐1 knockout mice and tranfected them with wild‐type and mutated forms of syndecan‐1 using lentiviral vectors. Wild‐type, syndecan‐1 knockout and mutated syndecan‐1 overexpressing mouse vascular smooth muscle cells were cultured in plates with collagen coated silicone membranes. The cells were then subjected to 10% strain at 1 Hz biaxial or uniaxial loads for up to two hours. We found that syndecan‐1 knockout or deletion of the cytoplasmic region of syndecan‐1 caused an increase in actin stress fibers and focal adhesion sites in response to mechanical strain. Further, knockout of syndecan‐1 led to enhanced ERK and Src phosphorylation in response to mechanical strain. These findings support that syndecan‐1 is an important mediator of mechanotransduction in vascular cells.