High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase

Area of Science:

• Cardiovascular Biology
• Lipid Metabolism
• Endothelial Function

Background:

• Atherosclerosis is a leading cause of cardiovascular disease.
• High-density lipoprotein (HDL) cholesterol levels are inversely related to atherosclerosis risk.
• The atheroprotective mechanisms of HDL are not fully understood.

Purpose of the Study:

• To investigate the mechanism by which HDL exerts its atheroprotective effects.
• To determine if HDL stimulates endothelial nitric oxide synthase (eNOS).
• To identify the HDL receptor and apolipoproteins involved in eNOS activation.

Main Methods:

• Experiments using cultured endothelial cells and Chinese hamster ovary cells expressing scavenger receptor-BI (SR-BI).
• Analysis of eNOS activation in isolated endothelial cell caveolae and plasma membranes.
• Assessment of endothelium-dependent relaxation in mouse aortae from wild-type and SR-BI knockout mice.

Main Results:

• HDL, but not its major apolipoproteins or LDL, stimulates eNOS in endothelial cells.
• SR-BI mediates HDL-induced eNOS activation.
• HDL enhances nitric oxide-dependent relaxation in wild-type mouse aortae, but not in SR-BI knockout aortae.
• ApoA-I binding is required for HDL activation of eNOS.

Conclusions:

• HDL activates eNOS through SR-BI, a process dependent on ApoA-I.
• Increased nitric oxide production by HDL may be a key factor in its atheroprotective properties.
• SR-BI plays a critical role in mediating the vascular protective effects of HDL.