Sign
out: Cardiovascular Pathology and Autopsy
Pathology.
Atherosclerosis is the principal cause
of heart disease and a leading cause of stroke, making
it the most common cause of death in the U.S. The
laboratory is seeking to understand the biochemical
processes resulting in atherosclerosis in order to
combat this pervasive disease. Atherosclerosis is
characterized by the development of necrotic/lipid
cores within the intima of arteries at particular
sites in the circulation. These necrotic/lipid cores
form in the setting of a pre-existing intimal hyperplasia,
characterized by the proliferation of smooth muscle
like cells in the intima. The laboratory is investigating
both the signal transduction mechanisms responsible
for the pre-atherosclerotic intimal hyperplasia as
well as the factors stimulating the formation of intimal
necrotic/lipid cores.
Essentially all risk factors for atherosclerosis
result in the enhanced generation of hydrogen peroxide
in the vessel wall by the activation of membrane bound
NADPH oxidases. These low physiologic levels of hydrogen
peroxide are mitogenic, stimulating vascular cell
growth and proliferation. The mechanisms by which
low endogenous levels of hydrogen peroxide stimulate
cellular proliferation are currently poorly understood.
The laboratory is using proteomic approaches with
cultured vascular cells to identify signal transduction
pathways activated by low physiologic levels of hydrogen
peroxide.
Intimal hyperplasia, the pre-cursor
lesion for atherosclerosis, forms both in vessels
that are prone to develop atherosclerosis and in vessels
remarkably resistant to atherosclerosis. The laboratory
is using proteomic approaches to identify and characterize
the components of intimal hyperplasia specific to
atherosclerosis-prone arteries to elucidate the mechanisms
leading to the formation of the necrotic/lipid cores
characteristic of atherosclerosis.
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