Atherosclerosis Linked to Failure of Local Anti-Inflammatory Response

Cardiovascular disease researchers have linked the development of atherosclerosis to the failure of sites in the arteries to produce anti-inflammatory factors that would otherwise resolve points of local inflammation.

Investigators at Baylor College of Medicine (Houston, TX, USA) based their study on recent findings that acute inflammation does not simply passively resolve but is actively terminated by a homeostatic process that is governed by specific lipid-derived mediators initiated by lipoxygenases. They tested this hypothesis by analyzing apolipoprotein E-deficient mice with 1) global leukocyte 12/15-lipoxygenase deficiency, 2) normal enzyme expression, or 3) macrophage-specific 12/15-lipoxygenase overexpression.

Results published in the June 17, 2008, online edition of the Journal of the Federation of American Societies for Experimental Biology (FASEBJ) indicated that 12/15-lipoxygenase expression protected mice against atherosclerosis via its role in the local biosynthesis of lipid mediators, including lipoxin A4, resolvin D1, and protectin D1. These mediators exerted potent agonist actions on macrophages and vascular endothelial cells that could control the magnitude of the local inflammatory response.

"Inflammation is a two-edged sword. If resolution fails and the response gets out of hand there is a never ending civil war in the body,” said first author Dr. Aksam J. Merched, assistant professor of molecular and cellular biology at Baylor College of Medicine. "Continued inflammation draws more macrophages (potent immune system cells) to the site of the inflammation. They produce molecules that turn this into a vicious cycle.”


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