Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice

作者：Xu, Xiangbin; Gao, Xue; Potter, Barry J.; Cao, Ji-Min; Zhang, Cuihua^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2007, 27(4): 871-877.

DOI：10.1161/01.ATV.0000259358.31234.37

• atherosclerosis
• coronary artery disease
• endothelial function
• microcirculation
• reactive oxygen species

Background - We hypothesized that atherosclerosis inhibits NO-mediated endothelium-dependent dilation of coronary arterioles through interaction of ox-LDL with its receptor, LOX-1, through the production of O(2)y(-) in endothelial cells.
Methods and Results - We assessed the role of ox-LDL in endothelial dysfunction in a murine model of atherosclerosis ( ApoE KO mice). Coronary arterioles from WT control and ApoE KO mice were isolated and pressurized without flow. Although dilation of vessels to endothelium-independent vasodilator SNP was not altered between ApoE KO and WT mice, dilation to the endothelium-dependent agonist, ACh was reduced in ApoE KO versus WT mice. Impaired vasodilation to ACh in ApoE KO mice is partially restored by NAD(P) H oxidase inhibitor, apocynin or DPI. Messenger RNA expression for NAD(P) H oxidases was higher in ApoE KO mice than that in WT and anti-LOX-1 treated ApoE KO mice. Anti - LOX-1, given in vivo, restored NO-mediated coronary arteriolar dilation in ApoE KO mice, but did not affect the endothelium-dependent vasodilation in controls.
Conclusions - These results suggest that ox-LDL impairs endothelium-dependent NO-mediated dilation of coronary arterioles by activation of a signaling cascade involving LOX-1 and NAD(P) H oxidase expression.

• 出版日期2007-4
• 单位中国医学科学院北京协和医院