| Mol Cell Endocrinol. 2006 Apr 27; [Epub ahead of print] |
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| The 5 lipoxygenase system in the vasculature: Emerging role in health
and disease. |
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| Osher E, Weisinger G, Limor R, Tordjman K, Stern N. |
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| Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv
Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv, Israel. |
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| 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. |
