Our laboratory has investigated the vascular response to pathophysiologically relevant stimuli. We have recently extended these studies to examine mechanisms through which the amyloid-beta peptide affects properties of vasculature and neurons.
AGEs also accumulate in atherosclerotic vasculature, amyloidoses, and renal failure.
We have identified a critical cellular receptor, termed RAGE, which mediates the effects of AGEs on cellular elements. Molecular characterization of RAGE employs genetically manipulated animals, identification of proteins which bind to the RAGE cytosolic tail, characterization of factors regulating RAGE expression at the transcriptional level, and study of the effect of blocking RAGE for the development of diabetic complications. Properties of hypoxic vasculature have been analyzed based on the hypothesis that mechanisms set in motion during oxygen deprivation prime blood vessels for processes triggered when reoxygenation occurs. Our analysis of hypoxic vas-culature has focussed on changes in gene expression, especially those which influence thrombogenicity and leukocyte interactions. We have identified a pathway through which oxygen deprivation promotes the activation of coagulation through coordinated induction of procoagulant and suppression of anticoagulant activities.