It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated pro-inflammatory disorders, including cancer, neurodegenerative diseases, and atherosclerosis.
ALOX5 gene variants do not appear to be related to clinical CHD events or subclinical atherosclerosis regardless of bioavailable enzyme substrate levels in this multiethnic cohort.
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.
Inhibiting the 5-lipoxygenase pathway through either leukotriene synthesis inhibitors or leukotriene receptor antagonists in experimental models of atherosclerosis has however generated contradictory results.
Using a pathway-based approach, we also detected statistical evidence for interactions among ALOX5, ALOX5AP and LTA4H using RNA expression data from a collection of freshly harvested human aortas with varying degrees of atherosclerosis.
Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis.
The 3 and 4 variants lead to higher 5-LO expression and provide additional evidence that these alleles are associated with greater risks of atherosclerosis and MI in the context of a high-AA diet.
The 3 and 4 variants lead to higher 5-LO expression and provide additional evidence that these alleles are associated with greater risks of atherosclerosis and MI in the context of a high-AA diet.
We previously used an integrative genetics approach to demonstrate that 5-lipoxygenase (5-LO) deficiency in mice (Alox5 (-/-)) protects against atherosclerosis despite increasing lipid levels and fat mass.
Human and animal studies have suggested a role for the ALOX5 gene in atherosclerosis, including a significant association between a promoter polymorphism and a carotid intimal-medial thickness in response to dietary fat.
Studies in mice followed by several extensive clinical studies have identified ALOX5 and ALOX5AP polymorphisms as strong risk factors for atherosclerosis and cerebrovascular pathologies.
In contrast to human plaques, levels of 5-LO mRNA are not significantly increased in plaque tissues from two atherosclerosis-prone mouse strains, and mouse plaques exhibit segregated cellular expression of LTA4H and 5-LO as well as strong increases of CysLT1 and CysLT2 mRNA.
The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis.
We determined 5-lipoxygenase genotypes, carotid-artery intima-media thickness, and markers of inflammation in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study.
Studies of the 5LO pathway in other disease areas suggest that 5LO could contribute to atherosclerosis at different levels, such as lesion initiation, growth and cellular proliferation within the lesion, and/or destabilization of plaques that can lead to their rupture.