Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties.

Cardiovascular Division, *Department of Medicine and {Department of Biochemistry and Molecular Biophysics, WashingtonUniversity School of Medicine, St. Louis MO 63110; {Departments of Artherosclerosis Therapeutics, }Biochemistry and}Chemistry Parke-Davis, Ann Arbor MI 48105 and #Department of Pharmacology, Columbia University, New York, NY 10032,U.S.A.1 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of itslocalization in lesions and the many biological activities exhibited by its products. To provide furtherevidence for a role of 15-LO, the e•ects of PD 146176 on the development of atherosclerosis incholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro andlacks significant non specific antioxidant properties.2 PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K