Signaling by scavenger receptor BI (SR-BI), the high affinity receptor for HDL
Our prior studies indicated that SR-BI uniquely serves as a cholesterol sensor on the endothelial cell plasma membrane, yielding potent beneficial changes in endothelial cell phenotype which may underlie the antiatherogenic properties of HDL. Using mutagenesis and structure-function analysis, the molecular underpinnings cholesterol sensing and resulting signal initiation are being pursued. These include studies of the SR-BI adaptor molecule PDZK1. Recent work in PDZK1 null mice indicated that the molecule is critically involved in optimal responses to vascular injury. The ultimate goal is to determine if the functions of the SR-BI/PDZK1 tandem in endothelium can be targeted to prevent or treat cardiovascular disease.