15-lipoxygenase inhibitors as anti-atherosclerosis agents.
15-lipoxygenase (15-LO) has been implicated in the process of atherogenesis. Numerous studies have suggested a role for this enzyme in lipoprotein oxidation and modification, resulting in the generation of an LDL particle that is avidly metabolized by monocytes/macrophages. Whilst biochemical studies have demonstrated the induction of 15-LO by cytokines, in vivo work has shown that the induction of the enzyme alone is not sufficient to promote lesion formation. The discovery of novel and specific inhibitors of 15-LO, in addition to animals created using genetic technologies, is allowing the evaluation of this hypothesis in vivo.
Cornicelli
J A
JA
Parke-Davis Pharmaceutical Research Division, The Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. Cornicj@aa.wl.com