Wall shear stress promotes intimal hyperplasia through the paracrine H2O2-mediated NOX-AKT-SVV axis
Haolong Zhang1, Zhipeng Yang2, Jing Wang3
1Department of Vascular Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Aims:
Oscillatory wall shear stress (WSS)-linked oxidative stress promotes intimal hyperplasia (IH) development, but the underlying mechanisms are not completely understood.
Materials And Methods:
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.
Key Findings:
Our in vitro study suggested that H2O2 promoted proliferation and migration while suppressing apoptosis in cultured human umbilical vascular endothelial cells.
Significance:
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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