Research in our laboratory centers on the molecular mechanisms of atherosclerotic foam cell development. In particular, we have focused on the means by which macrophages and vascular smooth muscle cells, the principal lipid accumulating cells of the atherosclerotic lesion, bind and internalize oxidized lipoprotein, the principle of pathologic lipid in atherosclerosis. We study three major lipoprotein receptors; the low density lipoprotein (LDL)-receptor, the "class A" scavenger receptors, and CD36, a newly recognized "class B" scavenger receptor. We are currently studying:

1) The effect of cytokines, growth factors, and lipid itself on expression and transcriptional regulation of the LDL receptor and scavenger receptors. Modulation of receptor expression is evaluated as a potential means to prevent lipid accumulation in atherosclerosis.

2) The role of CD36 in the uptake of oxidized LDL by macrophages. We are evaluating domains of CD36 which recognize oxidized LDL as well as epitopes of the lipoprotein which interact with the receptor. We examine human tissue and animal models of atherosclerosis to determine receptor expression by immunohistochemistry. Collaborative studies are in progress to generate CD36 "knockout" mice. These mice will be crossbred with atherosclerosis-prone mice to determine the relative importance of the receptor in atherosclerotic lesion development.