This transcriptional activation was associated with the binding of HIF-1 to the FLAP promoter and was strongly associated with atherosclerosis lesion size.
The 5-lipoxygenase activating protein (FLAP), encoded by the activating 5-lipoxygenase (ALOX5AP) gene, is a crucial mediator of the biosynthesis of leukotrienes, which have been implicated in atherosclerosis.
Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes.
Recently, leukotriene-based inflammation has also been shown to play an important role in atherosclerosis: ALOX5AP and LTA4H, both genes in the leukotriene biosynthesis pathway, have individually been shown to be associated with various cardiovascular disease (CVD) phenotypes.
Studies in mice followed by several extensive clinical studies have identified ALOX5 and ALOX5AP polymorphisms as strong risk factors for atherosclerosis and cerebrovascular pathologies.