ABSTRACT Evidence suggests that excessive proliferation and migration of vascular smooth muscle cells are key events in the development of atherosclerosis as well as restenosis after balloon angioplasty. These processes are mainly mediated by growth factors, cytokines and related factors released by various cells in the vessel wall. The mechanisms of action of these factors are however not very clear. Vascular smooth muscle cell growth factors and cytokines can activate phospholipases with the release of lipids such as arachidonic and linoleic acids, which can be further metabolized by several pathways including the lipoxygenase pathway. These oxidative pathways can lead to the formation of free radicals and lipid peroxides. Lipoxygenase products have been shown to have potent inflammatory, growth and chemoattractant effects in cells. This chapter reviews the role and mechanisms of action of the lipoxygenase pathway in mediating growth and chemotactic effects of cytokines, growth factors and high glucose in vascular smooth muscle cells. Activation of the lipoxygenase pathway and associated oxidant stress may be a common mechanism shared by these factors in leading to increased inflammatory and proliferative disorders, including those associated with diabetic vascular complications.
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