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Huang, Hua (2014): Inducible Nitric Oxide Synthase inhibits macrophage migration,a potential explanation for iNOS's proatherosclerotic action. Dissertation, LMU München: Faculty of Medicine



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.