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M. FRESNO Y COLS. AN. R. ACAD. NAC. FARM

leading to an inflammation in the intima of large arteries and involving
several cell types including immune cells as T lymphocytes and
monocytes/macrophages as well as endothelial and smooth muscle cells
and platelets (69, 70). Among those, monocytes/macrophages play an
important key role in many phases of atherogenic process. Thus, after an
atherogenic stimulus, monocyte-macrophages reversibly adhere to the
endothelium and migrate across it, leading to a prolonged retention of
those cells in the intima which is central in atherogenesis. A variety of
substances including prostanoids have been implicated in the
pathogenesis of atherosclerosis.

Prostanoids may be involved in atherosclerosis through their
ability to regulate a variety of mechanisms potentially involved in the
pathogenesis such as inflammation, vasodilatation, vasoconstriction,
platelet aggregation and leukocyte–endothelial cell adhesion, and
leukocyte migration among others (71, 72). In this regard, COX-2
expression has been observed in symptomatic atherosclerotic lesions (73).
This enzyme may play a dual role in the pathogenesis of the
atherosclerosis. Initially, COX-2 expression is induced in monocytes by
pro-inflammatory cytokines and several growth factors. Then, COX-2-
mediated PG production by activated macrophages may promote
atherosclerosis in the artery wall through several mechanisms, as
induction of other proinflammatory mediators or by favouring migration
of macrophages and other immune cells or by induction of adhesion
molecules. Later on, COX-2-derived PGI2, likely from the endothelial
cells, may have a protective role in atherogenesis by favouring
vasodilatation. Moreover, in atherosclerotic patients, PGI2 can be formed
through the action of both COX-1 and COX-2 (54). COX-1 but not COX-
2 is expressed in normal arteries, whereas both isoforms are expressed in
atherosclerotic lesions. In those lesions COX-2 is expressed not only by
monocyte/macrophages, but also by endothelial and proliferating smooth
muscle cells (7). Atherogenic lipoproteins, such as oxidized low density
lipoproteins (oxLDL) may promote atherosclerosis first by contributing to
inflammation by activating monocytes/macrophages and later by
stimulating lipid uptake by macrophages, leading to foam cell formation.
Interestingly, oxLDL has apparently contradictory effect on macrophages,
since they can activate the expression of some pro-inflammatory genes

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