Endothelial Underpinnings of Atherosclerosis

Although it has been recognized for many years that atherosclerosis, which underlies disorders such as myocardial infarction and stroke, is initiated by low-density lipoprotein (LDL) cholesterol passage into the artery wall and its engulfment by macrophages, it was unknown how LDL enters the artery wall to instigate atherosclerosis. We recently discovered that the endothelial LDL transport that underlies atherosclerosis is mediated by scavenger receptor class B type I (SR-BI). We currently are investigating how SR-BI serves this function, and how SR-BI expression is regulated in endothelial cells. We are also interrogating the processes that promote or attenuate the vascular inflammation that comprises the second major process underlying atherogenesis. Present efforts include a project determining how hypercholesterolemia initiates vascular inflammation independent of other disease risk factors.

Incorporation of circulating LDL (red) into the aorta of a normal mouse (nuclei are blue)

Circulating LDL incorporation into the aorta of a mouse lacking SR-BI in endothelial cells

Rolling fluorescent-tagged leukocytes in microvasculature of mouse with normal leukocyte-endothelial cell adhesion

Rolling leukocytes in mouse with increased leukocyte-endothelial cell adhesion