Newly Discovered Drug Reduces Heart Enlargement, Study Shows

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Newly Discovered Drug Reduces Heart Enlargement, Study Shows

January 28, 2009

Researchers at the University of California, Davis, have discovered that a prototype drug made at UC Davis reduces heart enlargement, one of the most common causes of heart failure, which affects 5 million people in the United States and contributes to 300,000 deaths annually.

The research showed that the prototype drug, similar to compounds being tested in clinical trials, reduces heart swelling in rats with heart failure. The drug, known as TUPS, is known as an epoxide hydrolase enzyme inhibitor.

Findings from the study, conducted in the laboratories of cardiologist and cell biologist Nipavan Chiamvimonvat of the UC Davis School of Medicine and entomologist Bruce Hammock, were published in the Jan. 13 issue of the Proceedings of the National Academy of Sciences. Ding Ai of Beijing, lead author on the paper, previously worked as a Ph.D. student in the Chiamvimonvat and Hammock laboratories. The work was done in collaboration with John Shyy at UC Riverside and Yi Zhu of Peking Medical University.

"The study of rat models showed that heart failure is driven by high levels of a compound called angiotensin, which is associated with high blood pressure, artery disease and some kidney disease,” Hammock said. “When that occurs, a key enzyme called soluble epoxide hydrolase is increased."

“Soluble epoxide hydrolase,” Chiamvimonvat said, “degrades anti-inflammatory and anti-hypertensive factors normally in the heart and blood, which may contribute to the pathological progression of heart failure.”

Heart failure weakens the heart's pumping ability, she said. Blood and fluid can back up into the lungs; accumulate in the feet, ankles and legs (edema); and result in tiredness and shortness of breath. Coronary artery disease, high blood pressure and diabetes are the leading causes of heart failure.

In earlier studies, the Chiamvimonvat and Hammock laboratories showed that the chemical mediators, which soluble epoxide hydrolase degrades, block and reduce heart enlargement and irregular heart rhythms in a mouse model. The more recent work with TUPS extends these studies to show the role that soluble epoxide hydrolase plays in these angiotensin-triggered heart problems, and the possibilities for preventing heart failure with drugs that block the activity of soluble epoxide hydrolase and allow the inhibitors to do their heart-protective work.

The initial research on the enzyme sprang from studies on insect pest control in the Hammock lab.

The latest research is funded in part by the National Science Foundation of China; the Major National Basic Research Grant of China; National Institute of Environmental Health Sciences, National Institutes of Health, and by the National Heart, Lung, and Blood Institute Ruth L. Kirschstein National Service Award.

A more detailed description of the research is available online at http://entomology.ucdavis.edu/news/heartresearchdrug.html.
Media contact(s):

    * Bruce Hammock, Entomology, (530) 752-7519, bdhammock@ucdavis.edu
    * Kathy Garvey, Entomology, (530) 754-6894, kegarvey@ucdavis.edu
    * Pat Bailey, UC Davis News Service, (530) 752-9843, pjbailey@ucdavis.edu
http://www.news.ucdavis.edu/search/news_detail.lasso?id=8978