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Updated: Jul 17, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice
Xiangbin Xu1, Xue Gao, Barry J Potter
1Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA.
Insights
Atherosclerosis impairs nitric oxide-mediated coronary artery dilation via oxidized low-density lipoprotein (ox-LDL) interacting with LOX-1 and activating NAD(P)H oxidase. Blocking LOX-1 restores normal dilation in atherosclerotic mice.
Area of Science:
- Cardiovascular Biology
- Endothelial Function
- Atherosclerosis Research
Background:
- Atherosclerosis is linked to impaired nitric oxide (NO)-mediated endothelium-dependent dilation in coronary arterioles.
- Oxidized low-density lipoprotein (ox-LDL) interaction with its receptor LOX-1 may cause endothelial dysfunction via reactive oxygen species production.
Purpose of the Study:
- To investigate the role of ox-LDL in endothelial dysfunction in a murine model of atherosclerosis.
- To determine the involvement of LOX-1 and NAD(P)H oxidase in ox-LDL-induced impairment of NO-mediated vasodilation.
Main Methods:
- Utilized apolipoprotein E knockout (ApoE KO) mice as a model for atherosclerosis.
- Isolated and pressurized coronary arterioles from ApoE KO and wild-type (WT) mice.
- Assessed vasodilation to endothelium-dependent (acetylcholine) and independent (SNP) vasodilators.
- Investigated the effects of NAD(P)H oxidase inhibitors (apocynin, DPI) and anti-LOX-1 treatment.
Main Results:
- ApoE KO mice exhibited reduced acetylcholine-induced vasodilation compared to WT mice, while SNP-induced dilation was similar.
- Impaired vasodilation in ApoE KO mice was partially restored by NAD(P)H oxidase inhibitors.
- LOX-1 expression was upregulated in ApoE KO mice, and in vivo anti-LOX-1 treatment restored NO-mediated dilation.
Conclusions:
- Oxidized low-density lipoprotein (ox-LDL) impairs endothelium-dependent, NO-mediated coronary arteriolar dilation.
- This impairment involves a signaling cascade initiated by LOX-1 activation and subsequent NAD(P)H oxidase expression.
- Targeting LOX-1 may represent a therapeutic strategy to improve endothelial function in atherosclerosis.
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 O2ÿ- 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.
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