Impairment of Reverse Cholesterol Transport System and Atherosclerosis

摘要: High density lipoprotein (HDL) derives cholesterol from peripheral tissues, and is esterified by lecithin:cholesterol acyltransferase (LCAT), forming cholesteryl ester (CE). HDL serves as a carrier of tissues to the liver for excretion into bile. This system was designated “ reverse transport”, which protects against atherosclerosis. Plasma transfer protein (CETP) promotes CE apolipoprotein (apo) B-containing lipoproteins such very low (VLDL) (LDL). Since CETP reaction theoretically reduces plasma HDL-cholesterol increases VLDL LDL-cholesterol, has been considered be proatherogenic factor its deficiency presumed an anti-atherogenic state. However, discovery CETP-deficient subjects detailed analysis metabolism in these patients revealed important roles both LDL particles transport system. causes variety abnormalities concentration, composition functions LDL. Our vitro study demonstrated that large CE-rich particles, accumulate subjects, have impaired ability efflux lipid-laden macrophages. The addition induced formation small high (VHDL) enriched with phospholipids. These VHDL had potent antiatherogenic function when incubated acetyl-LDL loaded Furthermore, our recent epidemiological studies increased incidence atherosclerosis coronary carotid arteries subjects. Two common mutations identified deficiency; one G-to-A mutation at 5’ splice donor site intron 14 other missense (D442:G). We found gene extremely frequent Omagari area Akita Prefecture. Epidemiological this are not accompanied longevity atherosclerotic cardiovascular diseases can often develop patients. Therefore, marked hyperalphalipoproteinemia due may state, suggesting importance analyzing vivo.