Researchers Paving the Way for New Heart Disease Treatments (8/5/2008)

University of Arizona researchers have increased their understanding of a chemical that regulates everything from blood flow and wound healing to lung function and memory formation. Their work may one day pave the way for new treatments for heart disease and other illnesses.

William Montfort, a professor in the UA department of biochemistry at a member of the BIO5 Institute, collaborated with researchers working with insects to produce a protein called soluble guanyl cyclase in the lab. Soluble guanyl cyclase, known as sGC, occurs naturally in our bodies; it is important because it binds to and regulates a remarkably versatile chemical called nitric oxide. Nitric oxide is found in our bodies as well.

"Our cells use it to regulate huge amounts of our physiology," Montfort said. Among other things, nitric oxide is also the active ingredient in nitroglycerin, which has long been manufactured as a drug to relax blood vessels and control the chest pain associated with heart disease.

By better understanding the workings of sGC, scientists can potentially better understand how nitric oxide works as well. Yet producing enough sGC to study in the lab has long been a challenge, because the genes that produce sGC in humans don't produce much of it, at least not in a stable form.

Humans aren't the only ones who produce sGC and nitric oxide. Montfort learned that a colleague in the Arizona Research Laboratories neurobiology division, associate professor Alan Nighorn, was studying sGC in hawkmoths, where nitric oxide regulates odor detection.

Working collaboratively, Montfort and Nighorn's labs succeeded in producing the hawkmoth protein in larger quantities. Their research was published in this month's issue of the Journal of Biological Chemistry.

Now that sGC is available in sufficient quantities, Montfort's lab plans to map its atomic structure in intricate detail and search for compounds that stimulate its activity. They'll use what they learn to then try to develop drugs that mimic aspects of nitric oxide's behavior. Such drugs could one day provide heart patients with alternatives to nitroglycerin, which loses effectiveness over time. Montfort's work is funded through 2013 by grants form the National Institutes of Health totaling $2.5 million.

"The research highlights what works so well at universities like ours, where we have broad-based science on a single campus," Montfort said. "The UA works hard to lower the barriers between departments and encourage multidisciplinary work. There's a long history of collaboration here."

The work also highlights the UA's commitment to training graduate students in multidisciplinary research. The first author on the paper, Xiaohui Hu, is one of Montfort's graduate students â€" and a part of the UA's biological chemistry program, which is designed to facilitate collaborative work among chemists, biochemists and medicinal chemists. "I challenged Xiaohui Hu with this project, which is really a very difficult one, and he grabbed hold and pushed it forward with gusto and imagination," Montfort said.

The paper also brings out the critical role that basic research plays in our larger lives. "By trying to understand scent sensing in an insect we gained the tools to try to develop new drugs that will be important to human health. You never know from where important insights are going to come," Montfort said.

Note: This story has been adapted from a news release issued by the University of Arizona

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