A miniature swine model of atherosclerosis:
Quantification of
naturally occurring biochemical promoters of atherosclerotic lesions.
David
B Sikes*, James R Turk, M. Harold Laughlin
This project supported by Merck-Merial, Dept of
Biomedical Science, Dept of Veterinary Pathobiology, The Dalton Cardiovascular
Research Center, University
of Missouri, College of Veterinary Medicine, and NHLBI PO2 HL52490
VVG
Cardiovascular disease is the leading cause of morbidity and mortality in the
United States. Atherosclerosis, the process of thickening and hardening of the
arteries is a substantial contributor to cardiovascular disease. Within twenty
weeks of a high fat, high cholesterol diet combined with a sedentary lifestyle
atherosclerotic lesions are commonly seen in the femoral and carotid arteries
of Yucatan miniature swine. The purpose of this study is to look at the
initiation and progression of atherosclerotic lesions. To achieve this we will
be using immunohistochemical (IHC) techniques to estimate the severity of
oxidative injury within the arterial wall.
Superoxide
Dismutase (SOD 1) converts superoxide
to hydrogen peroxide. Superoxide anion, a 1- electron reduction produce of
oxygen, is the primary source from which most other reactive oxidants are
derived from. Hypothesis: In diseased states
species. Hypothesis:
In diseased states the malondialdehyde level will increase in the vessel
wall.
4-Hydroxynoneanal- hypothesized
to play a key role in cell signal transduction, in a variety of pathways from
cell cycle events to cellular adhesion. Hypothesis: In
diseased states the 4-Hydroxynoneanal level will increase in the vessel wall.
Nitrotyrosine: With a
diminished SOD 1 capacity or the excess production of superoxide;
superoxide can combine with nitric oxide to form peroxynitrite a reactive
oxygen species which when exposed to tyrosine will form 3-Nitro-L-Tyrosine Hypothesis: In
diseased states there will be an increase in 3-Nitro-L-Tyrosine in the vessel
wall.
Oxidized
LDL plays a significant role in
atherogenesis and progression of atherosclerosis. Hypothesis:
In
Malondialdehyde the end produce of lipid peroxidation, by reactive oxygen
diseased
states there will be an increase in Ox-LDL in the vessel wall.
the SOD 1 level
will be increased in the vessel wall.