Atherosclerosis is a major cause of mortality and morbidity and many of the risk factors for this disease have been identified. What is not well understood is how the risk factors initiate and promote arterial lesion formation at the cellular and molecular levels; that is, the mechanisms that cause a response to injury at the vessel wall. Currently, we are studying the roles of proteins involved in the inflammatory like response of the vascular wall as well as the proteins involved in the tissue remodeling that results in an atherosclerotic lesion. These proteins include the matrix metalloproteinases, their natural inhibitors, other enzymes such as cyclooxygenase, and specific transcription factors. These are characterized for each of the major stages of lesion pathology. Much work is focused on how diet related risk factors such as hypercholesterolemia can promote lesion formation through effects on inflammatory processes and the mediators of these processes. Correlations are investigated between oxidized lipid products, extent and character of lesions, presence of markers of inflammation, proteins that remodel vascular tissue, and the transcription factors that may serve as a link between the initial injury and the proteins responsible for initiating and promoting arterial lesions. Miniature swine and hamsters are used for in vivo studies but many in vitro studies are conducted using endothelial cells, smooth muscle cells, monocytes, platelets and fibroblasts. Techniques include cell culture, electron microscopy, immunohistochemistry, in situ zymography, molecular techniques, biochemical assays, etc. Research is often conducted in collaboration with pharmaceutical or biotechnology companies to investigate the effects of new drugs on those aspects of atherosclerosis that are relevant to our investigations but we also collaborate with clinical researchers in Boston.
