[HDL metabolism in lifestyle-related illnesses]

Coronary artery disease (CAD) is a major public heath burden in many countries. HDL plays a critical role in cholesterol metabolism, so called reverse cholesterol transport (RCT). In RTC, HDL particles shuttle cholesterol from extra-hepatic tissues to the liver for excretion. Thus, enhanced RCT lowers total body cholesterol and thereby reduces the risk of developing CAD. We reported that human homologue of scavenger receptor of the class BI/CLA-1 (hSR-BI/CLA-1), like mouse SR-BI, functioned as a receptor for HDL. Hepatic hSR-BI/CLA-1 stimulates RCT, because it increases the hepatic uptake of free cholesterol from HDL. ABCA1 is a pivotal regulator of lipid efflux from cells to HDL particles, and plays an important role in RCT. Hyperglycemia is one of the risk factors for atherosclerosis. We showed that high glucose inactivated RCT via the inhibition of both hSR-BI/CLA-1 and ABCA1 expression. On the other hand, recent studies demonstrated that HDL binding to SR-BI activates eNOS, with the generation of nitric oxide, which may contribute to the positive cardiovascular effects. Treatment with angiotensin II reduced HDL-HDL-dependent eNOS activation via hSR-BI/CLA-1 expression, resulting in the progression of atherosclerosis. In conclusion, we demonstrate some mechanisms by which HDL is atheroprotective.