The 5 lipoxygenase system in the vasculature: emerging role in health and disease

Activation of the 5 lipoygenase (5LO) system within the vascular bed requires the presence of several cell types with distinct transcellular cross-talk mechanisms, resulting in the generation of 5LO produced metabolites and increased expression of receptors for these metabolites in vascular cells. The key products in this system, the leukotriens LTB4, LTC4 and LTD4, are potent mediators of vascular inflammation initiated by white blood cells and sustained or propagated thereafter through amplified metabolite generation and direct effects in endothelial and vascular smooth muscle cells. Leukotrienes act to enhance cell permeability and increase oxidative stress, vascular smooth muscle cell migration and arterial tone. 5LO activation is highly regulated, and is apparently both model/species-specific and region-specific. 5LO activation is also linked to plaque progression, plaque stability, activation of matrix metalloproteinases, propensity to coronary and cerebrovascular events and the evolution of aortic aneurysms. Genetic variants in the 5LO activating protein are strongly linked to increased cardiovascular risk and may serve as useful markers for future therapy targeting down regulation of 5LO expression and activity as a means to combat cardiovascular disease.