Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology
AUTOR(ES)
Trigatti, Bernardo
FONTE
The National Academy of Sciences
RESUMO
The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. Here we used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility. We also used SR-BI/apolipoprotein E double homozygous knockout mice to show that SR-BI can protect against early-onset atherosclerosis. Although the mechanisms underlying the effects of SR-BI loss on reproduction and atherosclerosis have not been established, potential causes include changes in (i) plasma lipoprotein levels and/or structure, (ii) cholesterol flux into or out of peripheral tissues (ovary, aortic wall), and (iii) reverse cholesterol transport, as indicated by the significant reduction of gallbladder bile cholesterol levels in SR-BI and SR-BI/apolipoprotein E double knockout mice relative to controls. If SR-BI has similar activities in humans, it may become an attractive target for therapeutic intervention in a variety of diseases.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17781Documentos Relacionados
- Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol
- Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI
- Scavenger Receptor BI (SR-BI) Clustered on Microvillar Extensions Suggests that This Plasma Membrane Domain Is a Way Station for Cholesterol Trafficking between Cells and High-Density Lipoprotein
- Regulation of SR-BI protein levels by phosphorylation of its associated protein, PDZK1
- Scavenger receptor class B, type I (SR-BI) is the major route for the delivery of high density lipoprotein cholesterol to the steroidogenic pathway in cultured mouse adrenocortical cells