Biomedical Engineering Reference
In-Depth Information
in comparison to controls. sVCAM-1 levels were not. h ese i ndings support
dif erent roles for sICAM-1 and sVCAM-1. sE-selectin and sICAM-1 may rel ect
ongoing atherosclerotic activity, while sVCAM-1 concentration is associated with
cumulative atherosclerotic burden.
sICAM-1 and Healthy Women
In the Women's Health Study, a study of healthy post-menopausal women,
C-reactive protein, sICAM-1, sE-selectin, and IL-6 were elevated among
women with a smoking history when compared to non-smoking controls. h ese
biomarkers remained elevated at er controlling for other risk factors for CVD,
including dyslipidemia, hypertension, diabetes, hormone replacement therapy,
and family history. Concentrations were more elevated in current compared to
former smokers. Individuals with any smoking history had higher concentrations
of these biomarkers than those with no smoking history (Bermudez
et al.
2002).
While circulating levels of adhesion molecules are elevated in individuals at
increased risk for CVD, they are biomarkers for systemic inl ammation and do
not directly confer risk. h e function of cellular adhesion molecules expressed on
endothelial cells provides insight on how circulating leukocytes gain entry into
tissues, allowing for inl ammatory injury. h e upregulation of ICAM-1 expression
is mediated via pro-inl ammatory cytokines, such as TNF-α and IL-6, and
enhances recruitment of circulating leukocytes out of the bloodstream, facilitating
migration into the subendothelium and initiating the generation of atherosclerotic
plaques.
Predictive Value of P-Selectin
P-selectin facilitates platelet-leukocyte interaction and the initiation of leukocyte
rolling along the endothelium. P-selectin concentration is elevated with acute
coronary syndrome and CHD (Blankenberg
et al.
2003, Güray
et al.
2004). h e
initial inl ammatory injury caused by cigarette smoke leads to elevations in sP-
selectin in addition to its inl uence on sICAM-1 expression.
Data from the Women's Health Study showed a strong correlation between
smoking status and sP-selectin. sP-selectin was also correlated with sICAM-1.
Healthy women with the highest levels of sP-selectin were at greatest risk of future
CVD. While correlated with sICAM-1, controlling for sICAM-1 in multivariate
analysis had minimal ef ect on the association between P-selectin and future
cardiovascular events, demonstrating the independence of these two biomarkers
(Ridker
et al.
2001).
