Biomedical Engineering Reference
In-Depth Information
cardiovascular risk and response to therapy. However, most of the current known
inflammatory biomarkers are not useful in screening for atherosclerotic disease.
C-reactive protein, sedimentation rate, and fibrinogen are not derived from the
vasculature and may signal inflammation in any organ. It is also possible that due
to heterogeneity among the population at risk, a single marker cannot provide suf-
ficient information for accurate prediction of disease. Therefore, there is a need for
identification of inflammatory markers that are more specific to vascular disease
and can be used for highly sensitive and specific assays capable of detecting and
quantifying atherosclerotic cardiovascular disease. Measurement of multiple circu-
lating disease-related inflammatory factors may be more informative, enabling the
early identification of vascular wall disease activity.
Lipid-Modified Proteins as Biomarkers of Atherosclerosis
The biological function of lipid-modified proteins depends on the identity of the
attached lipid. At least five different lipid modifications of cysteines, glycines, and
other residues on the COOH- and NH(2)-terminal domains have been described.
Available evidence suggests that lipid-modified proteins are directly involved in
different steps of the development of lesions of atherosclerosis, from leukocyte
recruitment to plaque rupture, and their expression or lipid modification are likely
altered during atherogenesis (Ferri et al.
2005
). Several lipid-modified proteins can
be used as biomarkers for atherosclerosis.
Lp-PLA2 as Biomarker of Atherosclerotic Heart Disease
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospho-
lipase A2 superfamily, a family of enzymes that hydrolyze phospholipids.
Circulating Lp-PLA2 is a marker of inflammation that plays a critical role in
atherogenesis; its inhibition may have antiatherogenic effects. Epidemiological
data have consistently demonstrated the association of increased levels of Lp-PLA2
with increased risk of coronary heart disease (Sudhir
2005
). Polymorphisms of the
Lp-PLA2 gene have been reported, with varying significance, in Japanese and
Caucasian populations. Overall, epidemiological studies suggest that measurement
of Lp-PLA2 in plasma may be a useful biomarker for identifying individuals at
high risk for cardiac events. PLAC test (diaDexus Inc) for detection of Lp-PLA2 in
plasma is effective as a predictive biomarker of risk for cardiovascular disease and
approved by the FDA.
Nitric Oxide Impairment and Atherosclerosis
The role of nitric oxide (NO) in the cardiovascular system and in atherosclerosis
has been described in detail in a special report (Jain
2010
). Many studies have
shown that NO is a major antioxidant that serves to block oxygen-free radicals,
which, among other things, create oxidized low-density lipoprotein (LDL) cholesterol
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