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Epoxide Hydrolase Inhibitors Effective for Cardiac Hypertrophy in Mice

Bruce D. Hammock, Ph.D.
University of California Davis
R37ES02710, P42ES04699, and P30ES005707

Cardiac hypertrophy is defined as a thickening the of the heart muscle often as a result of high blood pressure. The heart muscle grows larger to compensate for the added stress of pumping blood against the increased pressure. Over time this condition can result in a weakening of the heart and can lead to congestive heart failure. New research supported by NIEHS in the laboratory of Bruce Hammock at the University of California Davis sheds light on a possible treatment to prevent heart enlargement.

Previous work by Hammock and his collaborators demonstrated that inhibition of an enzyme called epoxide hyrodrolase lowered blood pressure and lessened kidney damage in a laboratory animal model. The new research findings show that epoxide hydrolase inhibitors block an immune system protein, known as NF-?B, known to play a role in cardiac hypertrophy and accompanying arrhythmia. The inhibitors were effective in preventing and reversing cardiac hypertrophy in a mouse model.

These findings show that by blocking the pathway leading to the overgrowth of cardiac muscle, preventing the progressive deterioration of heart function is possible. This work could lead to new therapies for treating enlarged hearts and heart arrhythmias­conditions that currently have more invasive treatment options and ultimately progress to heart failure and sudden cardiac death.

Citation: Xu D, Li N, He Y, Timofeyev V, Lu L, Tsai HJ, Kim IH, Tuteja D, Mateo RK, Singapuri A, Davis BB, Low R, Hammock BD, Chiamvimonvat N. Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18733-8.

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Last Reviewed: May 15, 2007