Inducible Nitric Oxide Synthase inhibits macrophage migration,a potential explanation for iNOS's proatherosclerotic action

Macrophage-derived foam cells play a critical role in all stages of
atherosclerosis, from the earliest discernable lesions to complex
plaques. oxLDL is thought to be a main trigger for endothelial
release of pro-inflammatory cytokines, subsequently causing
transmigration of the monocytes into the vessel wall. Moreover,
formation of macrophage-derived foam cells is mainly induced by
oxLDL. Deposition of macrophage-derived foam cells in the lesions
is induced by oxLDL uptake, as this uptake causes migratory arrest
of the cells. Therefore, reversion of migratory arrest of
macrophage-derived foam cells might enable these cells to leave the
plaques resulting in reduction of plaque sizes. Our results show
that iNOS participates in the mechanisms of oxLDL induced
inhibition of macrophage-derived foam cell migration. Inhibition of
iNOS expression completely reversed oxLDL mediated migratory arrest
of macrophage-derived foam cells. Inhibition of iNOS was associated
with enhanced phosphorylation of focal adhesion kinase (FAK) and
subseqent actin polymerization. Furthermore, the p-FAK triggered
increase in actin polymerization is dependent on iNOS mediated
increased oxidative stress. Our results suggest that iNOS may be an
interesting target gene to reverse the process of atherosclerosis.