SR-B1 and PDZK1: partners in HDL regulation

To outline the roles of SR-B1 and PDZK1 in hepatic selective HDL cholesterol uptake and reverse cholesterol transport and the consequences for atherosclerosis development.

Much of our understanding of the physiological roles of SR-B1 and PDZK1 in HDL metabolism and atherosclerosis comes from studies of genetically manipulated mice. These show SR-B1 and PDZK1 play key roles in HDL metabolism and protection against atherosclerosis. The recent identification of rare loss of function mutations in the human SCARB1 gene verifies that it plays similar roles in HDL metabolism in humans. Other rare mutations in both the human SCARB1 and PDZK1 genes remain to be characterized but may have potentially devastating consequences to SR-B1 function.

Identification of carriers of rare mutations in human SCARB1 and PDZK1 that impair the function of their gene products and characterization of the effects of these mutations on HDL cholesterol levels and atherosclerosis will add to our understanding of the importance of HDL function and cholesterol flux, as opposed to HDL-cholesterol levels, per se, for protection against cardiovascular disease.