Functional genomics of the human high-density lipoprotein receptor scavenger receptor BI: an old dog with new tricks. Curr Opin Endocrinol Diabetes Obes 2013 Apr;20(2):124-31
Date
02/14/2013Pubmed ID
23403740Pubmed Central ID
PMC3967407DOI
10.1097/MED.0b013e32835ed575Scopus ID
2-s2.0-84874949459 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
PURPOSE OF REVIEW: The athero-protective role of scavenger receptor BI (SR-BI) is primarily attributed to its ability to selectively transfer cholesteryl esters from high-density lipoproteins (HDLs) to the liver during reverse cholesterol transport (RCT). In this review, we highlight recent findings that reveal the impact of SR-BI on lipid levels and cardiovascular disease in humans. Moreover, additional responsibilities of SR-BI in modulating adrenal and platelet function, as well as female fertility in humans, are discussed.
RECENT FINDINGS: Heterozygote carriers of P297S, S112F and T175A-mutant SR-BI receptors were identified in patients with high HDL-cholesterol levels. HDL from P297S-SR-BI carriers was unable to mediate macrophage cholesterol efflux, whereas hepatocytes expressing P297S-SR-BI were unable to mediate the selective uptake of HDL-cholesteryl esters. S112F and T175A-mutant receptors exhibited similar impaired cholesterol transport functions in vitro. Reduced SR-BI function in P297S carriers was also associated with decreased steroidogenesis and altered platelet function. Further, human population studies identified SCARB1 variants associated with female infertility.
SUMMARY: Identification of SR-BI variants confirms the key role of this receptor in influencing lipid levels and RCT in humans. A deeper understanding of the contributions of SR-BI to steroidogenesis, platelet function and fertility is required in light of exploration of HDL-raising therapies aimed at reducing cardiovascular risk.
Author List
Chadwick AC, Sahoo DAuthor
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AtherosclerosisFemale
Fertility
Humans
Lipids
Lipoproteins, HDL
Male
Mutation
Platelet Activation
Polymorphism, Single Nucleotide
Scavenger Receptors, Class B