Biomedical Engineering Reference
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that damages the endothelium and leads to atherosclerosis. The measurement of
NO bioavailability is of great clinical interest in the assessment of vascular health.
However, NO is rapidly oxidized to form nitrite and nitrate and thus its direct detec-
tion in biological systems is difficult.
Oxygen Free Radicals as Biomarkers of Atherosclerosis
Excessive production and/or inadequate removal of ROS, especially superoxide
anion, have been implicated in the pathogenesis of many cardiovascular diseases,
including atherosclerosis, hypertension, diabetes, and in endothelial dysfunction by
decreasing NO bioactivity. Vascular aging may be related to oxidative stress. Age-
related morphologic changes in large resistance vessels include an intima-media
thickening, increased deposition of matrix substances, thus ultimately leading to a
reduced compliance. Vascular aging is mainly characterized by an impaired
endothelium-dependent vasorelaxation. The expression of endothelial nitric oxide
synthase (eNOS), producing vasodilatatory NO, is markedly upregulated with
increasing age. However, vasorelaxation is impaired, as the production of ROS
such as superoxide (O
2
-), concomitantly increases.
Proteomic Profiles of Serum Inflammatory Markers of Atherosclerosis
Protein microarray-based measurements of abundant circulating proteins have been
carried out to identify biomarkers of atherosclerotic disease. Using a longitudinal
experimental design with apoE-deficient mice and control serum protein expres-
sion of 30 inflammatory markers measured by protein microarray, a subset of pro-
teins was identified to predict severity of atherosclerotic disease with high level of
accuracy (Tabibiazar et al.
2006
). The top serum protein biomarkers in this study
cover a wide range of atherosclerotic biological process including macrophages
chemoattraction, T-cell chemokine activity, innate immunity, vascular calcification,
angiogenesis, and high fat-induced inflammation. The signature pattern derived
from simultaneous measurement of these markers, which represent diverse athero-
sclerosis-related biological processes, will likely add to the specificity needed for
diagnosis of atherosclerotic disease. The time specific vascular expression of these
markers was verified by showing their gene expression in the mouse aorta corre-
lated closely to the temporal pattern of serum protein levels. These data suggest that
quantification of multiple disease-related inflammatory proteins will provide a
more sensitive and specific method for assessing atherosclerotic disease activity in
humans, and identify candidate biomarkers for such studies. Because the vascular
tissue is not readily accessible, identification of protein markers in the serum can
have practical implications in developing diagnostic tools for diagnosis of coronary
artery disease in humans. A detailed microarray-based picture of the transcriptional
landscape in the diseased tissue would be useful for assessing upstream compo-
nents in the pathways that lead to inflammatory mediator expression, which is the
first step in developing highly targeted therapeutics. Serum biomarker assays can
then be used to assess the effects of such therapeutics.
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