Human Scavenger Receptor Class B Type I Variants, Lipid Traits, and Cardiovascular Disease

Over the years, pioneering work from Monty Krieger’s laboratory has solidified the role of scavenger receptor class B type I (SR-BI) as a physiologically relevant lipoprotein receptor, especially in mouse models.1,2 It is safe to conclude that the complete absence of SR-BI in mice is associated with significant increases in circulating high-density lipoprotein cholesterol (HDL-C) fractions of abnormal composition and size3; however, the effect of SR-BI-deficiency on circulating apoB cholesterol levels has not been extensively studied in mice or humans. This is an important point of emphasis given that, in comparison with mice, cholesterol transport in humans primarily resides in the apoB fractions.Article see p 838Although scavenger receptors are well characterized in cholesterol homeostasis, they have recently emerged as key mediators of a wide variety of systemic and cellular processes.4,5 The class B receptors include SR-BI, scavenger receptor class B type II, cluster of differentiation 36, and lysosomal integral membrane protein II. Human SR-BI is encoded by the SCARB1 gene on chromosome 12 and is expressed in many tissues and cell types, most notably in hepatocytes and steroidogenic cells. This integral transmembrane receptor has been demonstrated to interact with and mediate the selective uptake of cholesteryl esters from the major lipoprotein fractions; however, it is widely recognized as the primary receptor for HDL-cholesteryl ester uptake through selective core transfer.2 As such, SR-BI is a key regulator of systemic cholesterol levels, and SR-BI-deficiency results in hypercholesterolemia in mice and humans.3,6,7 Recently, we reported a novel role of SR-BI because HDL transfer of microRNAs to recipient cells is dependent on SR-BI.8 Genome-wide association studies have identified multiple common variants within SCARBI (introns and exons) that are significantly linked to circulating HDL-C levels9; however, …