herosclerosis is a chronic inflammatory disease

occurring preferentially in bifurcation

branching

and bending of blood vessels exposed to disturbed flow. Disturbed flow in atheroprone areas activates elevated proteases

degrading elastin lamellae and collagenous matrix

resulting in endothelial dysfunction and vascular remodeling. As a mediator for extracellular matrix protein degradation

cathepsin K (CTSK) was directly regulated by hemodynamics and contributed to atherosclerosis. The mechanism of CTSK responding to disturbed flow and contributing to disturbed flow-induced atherosclerosis is unclear. In this study

the partial carotid ligation model of mice and

in vitro

disturbed shear stress model were constructed to explore the contribution and potential mechanism of CTSK in atherosclerosis. Our results indicated that CTSK elevated in the disturbed flow area

in vivo

and

in vitro

along with endothelial inflammation and atherogenesis. Additionally

the expression of integrin αvβ3 was upregulated in these atheroprone areas. We found that inhibition of the integrin αvβ3-cytoskeleton pathway could significantly block the activation of NF-κB and the expression of CTSK. Collectively

our findings unraveled that disturbed flow induces increased CTSK expression

and contributes to endothelial inflammation and vascular remodeling

leading to atherogenesis eventually. This study is helpful to provide new enlightenment for the therapy of atherosclerosis.