The Effects And Potential Mechanisms Of Probucol On High-density Lipoprotein And Atherosclerosis In Hypercholesterolemic Rabbits

BackgroundAtherosclerotic diseases are the leading cause of death in developed countries and part of developing countries. Many epidemiological studies have revealed that low level of high-density lipoprotein cholesterol (HDL-C) is correlated with risk of atherosclerosis, indicating that HDL-C is "good" cholesterol. HDL has anti-atherogenic properties. However, the low concentration of HDL-C may not always be associated with atherosclerotic disease. One of the examples is the decrease in HDL-C value caused by probucol administration, which is associated with significant reduced coronary heart disease and restenosis after percutaneous coronary intervention. HDL mediates reverse cholesterol transport of cholesterol from atheroma foam cells and peripheral cholesterol to the liver and secreted, but the mechanisms of hepatic uptake and trafficking of HDL particles are poorly understood. The class B, type I scavenger receptor (SR-BI), the functional cell surface HDL receptor, binds HDL and mediates efficient lipid uptake and may play an important role in HDL metabolism and the atherosclerotic lesion. Evidence came from studies of mice and rats demonstrate that SR-BI is most abundantly expressed in the liver and steroidogenic tissues. Overexpression of SR-BI in the murine liver decreased HDL-C, accelerated HDL cholesteryl ester clearance and hepatic uptake, suggesting that SR-BI mediates HDL metabolism. However, the results of studies on the effect of probucol on the expression of SR-BI were controversy.The major pathways by which HDL protects against atherosclerosis, is believed to be related to its involvement in reverse cholesterol transport and anti-oxidant. Several enzymes associated with HDL have been postulated to be responsible for the anti-oxidative activity. Serum paraoxonase 1 (PON1), an HDL-bound antioxidant enzyme, plays a...