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New potential drug target for the treatment of atherosclerosis
Date:3/4/2008

roves hyperglycemia.

Cardiovascular disease is a leading cause of death in patients with metabolic syndrome, a clustering of obesity-related disorders including insulin resistance, hypertension, and dyslipidemia, says postdoctoral researcher and first author Grant D. Barish, M.D. Since PPAR delta plays a key role in fat metabolism and PPAR delta drugs can protect against obesity, we wanted to know whether activating PPAR delta would protect against atherosclerosis.

Atherosclerosis or hardening of the arteries" is a chronic disease in which high cholesterol levels coupled with inflammation lead to the build-up of fatty deposits, called plaque, on the inner walls of arteries. Eventually these plaques can limit blood flow, leading to angina, or they may rupture, resulting in blood clots that block arteries and cause heart attacks or strokes.

When the researchers fed an experimental drug that turns on PPAR delta to genetically altered mice that develop the characteristic plaques at an early age, especially when placed on a high-fat diet, mice developed 2530 percent fewer plaques. Further studies revealed that PPAR delta not only raises HDL levels but also suppresses the inflammatory response in the artery, dramatically slowing down lesion progression.

Barish and Evans also contributed to a related study, which was led by researchers at the University of California, Los Angeles and published in the same issue of PNAS. Using a different mouse model to mimic the development of atherosclerosis, the UCLA researchers detected an even more pronounced anti-inflammatory effect that slashed the number of aortic lesions by up to 70 percent.

While Barish, a clinically trained endocrinologist, cautions that extrapolating from mice to humans is inherently fraught with complications, he believes that drugs switching on PPAR delta have the potential to protect against obesity, insulin resistance and their associated cardiovascular risk
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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

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