Faculty Collaboration Database

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

02/14/2013

Pubmed ID

23403740

Pubmed Central ID

PMC3967407

DOI

10.1097/MED.0b013e32835ed575

Scopus ID

2-s2.0-84874949459 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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 D

Author

Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Atherosclerosis
Female
Fertility
Humans
Lipids
Lipoproteins, HDL
Male
Mutation
Platelet Activation
Polymorphism, Single Nucleotide
Scavenger Receptors, Class B