Wall shear stress promotes intimal hyperplasia through the paracrine H2 O2 -mediated NOX-AKT-SVV axis

Life Sciences
Haolong ZhangFangyu Zhu

Abstract

Oscillatory wall shear stress (WSS)-linked oxidative stress promotes intimal hyperplasia (IH) development, but the underlying mechanisms are not completely understood. We used an in vivo rabbit carotid arterial stenosis model representing different levels of WSS and found that WSS was increased at 1 month with 50% stenosis and was accompanied by VSMCs proliferation and interstitial collagen accumulation. Increased WSS promoted the expression of NOX, AKT, and survivin (SVV) and the proliferation/migration of VSMCs and reduced apoptosis. Our in vitro study suggested that H2O2 promoted proliferation and migration while suppressing apoptosis in cultured human umbilical vascular endothelial cells. We demonstrated that the elevation of WSS promotes VSMC proliferation and migration through the H2O2-mediated NOX-AKT-SVV axis, thereby accelerating IH development.

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