IDENTIFICATION OF 5-LIPOXYGENASE AS A MAJOR GENE CONTRIBUTING TO ATHEROSCLEROSIS

摘要

5-LO is expressed in the monocyte/macrophages (mono/mac) and foam cells of atherosclerotic lesions and is differentially expressed in CAST and CON6 mic e relative to B6 mice. Mice heterozygous for a null mutation of 5-LO, when placed on an LDLR-/- background, have dramatically reduced atherosclerosis a s compared to control LDLR-/- mice. In a genetic epidemiologic study, it is found that a common 5-LO polymorphism is strongly associated with carotid artery intima-media thickness (IMT). These results indicate that 5-LO is a major contributor to atherogenesis in animal models, and in atherosclerosis susceptibility in humans.