Biomedical Engineering Reference
In-Depth Information
intervention. Larger studies over extended periods are warranted for a conclusion
on whether n-3 PUFA exerts benei cial ef ects with respect to vascular disease by
modulation of CAMs.
INTRODUCTION
Over the past decades, increasing evidence has accumulated in support of an
inverse association between i sh consumption and mortality from ischaemic heart
disease (IHD). Large observational cohort studies and nested case control studies
have pointed at a reduction in cardiovascular mortality by i sh consumption, but
results are not entirely consistent (He
et al
. 2004). In large randomized controlled
trials, interventions with n-3 PUFA have improved the outcome in the primary
and secondary prevention of IHD (Lee
et al
. 2008), but not all trials have shown
positive ef ects. IHD mainly results from atherosclerosis of the coronary arteries,
and atherosclerosis is now considered, at least in part, an inl ammatory disease
of the arteries. h ere is evidence suggesting an anti-inl ammatory ef ect of n-3
PUFA (Calder 2006). One of the earliest events in atherogenesis is recruitment of
leucocytes/monocytes and their transendothelial migration and accumulation in
the vessel wall. h is process is predominantly mediated by CAMs that are expressed
on the vascular endothelium, platelets and circulating leucocytes in response to a
variety of inl ammatory stimuli. h e CAMs are transmembrane molecules, but a
soluble part can be measured in serum (sCAMs) and may serve as markers of the
inl ammatory state of the endothelium (Blankenberg
et al
. 2003).
During inl ammation a wide variety of cell-to-cell and cell-to-extracellular
matrix interactions are important. CAMs are transmembrane proteins located
on the cell surface that facilitate the transport of leucocytes through vascular
endothelium into the intima, where they participate in the formation and growth
of the atherosclerotic plaque. Expression of several CAMs has been reported
on established atherosclerotic lesions in humans (Huo and Ley 2001). Resting
endothelium does not support the adhesion of leucocytes under the shear stress
in arterial blood l ow. When the endothelium is activated through a variety of
inl ammatory mediators, the endothelial cells increase (or change) expression of
several CAMs, which makes the endothelium sticky to leucocytes (Huo and Ley
2001, Blankenberg
et al
. 2003). First, the leucocyte rolls and slows down along
the endothelial cell surface, mediated by the selectins. More i rm adhesion of the
leucocyte to the endothelium is mediated by ICAM-1 and VCAM-1. h e i nal step
is extravasation of the leucocyte.
Immunohistochemical analysis of human atherosclerotic plaques has shown
a strong expression of P-selectin by the endothelium overlying atherosclerotic
plaques characterized by inl ammation. However, this is not found in the normal
'healthy' arterial endothelium or in endothelium overlying i brous plaques.
P-selectin is also involved in the adhesion of platelets to monocytes and neutrophils,
playing a central role in neutrophils accumulation within thrombi. E-selectin is
