Biomedical Engineering Reference
In-Depth Information
almost absent on resting inactive epithelium, but spotty expression occurs on the
endothelium over i brous and lipid-containing plaques.
ICAM-1 and VCAM-1 belong to the immunoglobulin superfamily, a large
group of cell surface and soluble proteins involved in cell binding, adhesion and
recognition. Both ICAM-1 and VCAM-1 are expressed on the vascular endothelium
and by smooth muscle cells within the vascular wall. VCAM-1 expression is low in
healthy arteries but is concentrated (2-4 times) in the vascular epithelium overlying
the complicated atherosclerotic plaque. ICAM-1 is more abundantly expressed in
the vessel tree, and upregulation over complicated atherosclerotic plaques is much
less prominent (Duplaa
et al
. 1996). Moreover, i broblast and several cells in the
haematopoietic lineage may also express ICAM-1. h e biological role of sCAMs
is not clarii ed, but one study has suggested that sCAMs may inhibit monocyte
adhesion to activated endothelium, thus indicating a negative feedback mechanism
for monocyte adhesion (Abe
et al
. 1998).
CAMs AND ATHEROSCLEROSIS
h e evidence that CAMs play a role in atherogenesis derives from both animal
studies and
in vitro
studies. Genetically modii ed atherosclerotic animals lacking
the ability to express CAMs have markedly reduced atherosclerosis (Huo and Ley
2001). CAMs are expressed within the i rst week at er initiating an atherogenic
diet for experimental animals prone to developing atherosclerosis, and expression
of CAMs precedes the extravasation of monocytes in early atherosclerotic lesions
(fatty streaks). At later stages in the evolution of the complicated atherosclerotic
plaque in humans, CAMs might also recruit leucocytes through the neo-vasculature
in the intima underlying the plaque. h us, CAMs are critically involved in all
stages of atherogenesis (Huo and Ley 2001, Blankenberg
et al
. 2003). Furthermore,
sCAMs may be a good marker of atherosclerosis. We have previously reported a
positive association between sCAMs and the extent of atherosclerosis in a patient
referred for coronary angiography due to suspected angina pectoris (Eschen
et al
.
2005), as illustrated in Fig. 1. Studying endothelial cells
in vitro
has given insight
into the mechanisms by which n-3 PUFA may exert anti-inl ammatory and anti-
atherosclerotic ef ects. In cell cultures, n-3 PUFA reduce monocyte adhesion to
activated endothelial cells (De Caterina and Libby 1996, Sanderson and Calder
1998) and reduce expression of ICAM-1 and L-selectin on lymphocytes. DHA (De
Caterina and Libby 1996) and EPA have been demonstrated to reduce expression of
VCAM-1, ICAM-1 and E-selectin in cultures of human endothelial cells activated
by inl ammatory cytokines. h e magnitude of this decrease in sCAMs paralleled
the incorporation of DHA in the endothelium and a reduction in VCAM-1 mRNA
(De Caterina and Libby 1996). EPA and DHA may also produce anti-inl ammatory
ef ects through direct actions on the intracellular signalling pathways regulating
inl ammatory gene expression. One of the key transcription factors involved in the
expression of inl ammatory genes is nuclear factor kappa B (NF-κB). Studies have
shown that n-3 PUFA can downregulate the activity of NF-κB (Weber
et al
. 1995),
