Endothelial Basis for Thrombotic Disorders

Processes in the endothelium dictate the relative degree of thrombosis, which is often exaggerated in patients with a number of autoimmune conditions, and also underlies the acute clinical events characteristic of myocardial infarction and stroke. In studies of the thrombotic diathesis that occurs in individuals with the Antiphospholipid Syndrome (APS), we determined that APS-related autoantibodies promote thrombosis via the plasma membrane receptor apolipoprotein E receptor 2 (apoER2) in endothelial cells. We are presently investigating the participation of apoER2 in increased thrombosis risk independent of APS, possibly explaining the basis for certain genetic predispositions to myocardial infarction and cerebral vascular disease. Thrombosis is quantified in vivo in mice using intravital microscopy and underlying processes are interrogated by genetic manipulation in mice and experimentation in cell culture.

Circulating fluorescent-tagged platelets in microvasculature of mouse with normal thrombosis

Platelets forming large blood clots in mouse with increased thrombosis