Lipoxygenase pathways in atherogenesis

15-lipoxygeiiase-1 (also known as 12/15-LO in mice) and 5-LO/5-LO-activating protein (FLAP) cascades play central roles in low-density lipoprotein oxidation and leukotriene biosynthesis, respectively. Several genetic and expression studies unraveling an association of the 5-LO/ FLAP pathway to human cardiovascular disease have surfaced recently. Experimental studies in 12/15-LO knockout, 15-LO-1 transgenic, and 5-LO knockout mice on atherosclerotic backgrounds combined with gene expression data in human coronary artery disease have created compelling links that these pathways participate in the etiologic progression. However, a few conflicting studies and several unexplained mechanistic issues need to be resolved prior to assigning firm roles for LOs in cardiovascular disease. Development of novel pharmacologic tools to dissect the individual enzymes and receptors in the LO pathways should improve understanding of the individual components in the inflammatory aspects of atherosclerosis disease progression. (C) 2004, Elsevier Inc.