부산대학교 도서관

Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr Scarb1 mice, respectively, when compared to gender-matched Ldlr control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr Scarb1 mice compared to Ldlr control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr Scarb1 mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis. [ABSTRACT FROM AUTHOR]