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VOL. 74 (4) PROSTANOIDS ACTIONS IN CARDIOVASCULAR...

whereas reduce COX-2 expression (74). In agreement with this is the fact
that macrophage-derived foam cells from the atherosclerotic lesions in
mice, did not express COX-2. Thus induction COX-2 expression in
macrophages takes place before their transformation into foam cells in the
plaques.

In spite of the clear involvement of COX-2 derived prostanoids in
vascular atherosclerosis, results on the effect of COX-2 selective
inhibitors on the formation and progression of atherosclerotic plaques are
controversial. Results from different studies have shown increased,
reduced as well as unaltered atherogenesis (7, 62, 75-78). Those
discrepant effects of COX-2 may reflect the dual role of COX-2 in
promoting (early) but protecting later atherosclerotic lesions, mentioned
above. Results about the influence of COXs in atherosclerosis in animal
models, apart from those using pharmacological inhibitors, have been
obtained by means of cell transplantation from fetal liver or bone marrow
from COX-1 or COX- 2 deficient mice into ApoE or LDLR KO mice (75,
79, 80). The size of the atherosclerotic lesions was significantly reduced
when cells deficient in COX-2 were transplanted compared to the mice
transplanted with wild type fetal liver cells (75, 80). Those results
implicate COX-2 expression in the macrophage and not in other cells as
endothelial cells, smooth muscle cells, or T-cells in promoting
atherosclerotic lesion formation. Efforts to obtain information from mice
deficient in both COX-2 and ApoE or LDLR genes have been
unsuccessful due to the severe renal defects of COX-2 mice. Regarding to
COX-1, both proatherosclerotic and anti-atherosclerotic roles also have
been reported (79, 81).

Various prostanoids may play a significant role in the atherogenic
process (71, 82). Patients with extensive disease as well as murine models
of atherosclerosis have enhanced formation of TXA2. Even more, TP
antagonists decrease atherogenesis in mice. TP deficiency in
atherosclerotic mice models induced a significant delay in atherogenesis,
compared with mice deficient in apoE alone (72).

In contrast, PGI2 may theoretically have a beneficial effect in the
atherogenic process by limiting platelet adhesion to the endothelium and
activation in the plaques. In accordance with this, local delivery of PIGS
gene through an adenoviral vector reduces the platelet deposition seen

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