Better understanding of how this gene operates in the early stages of development may help researchers find better treatments for heart disease and cancer.

Using genetically engineered mice, researchers with the University of Minnesota Medical School's Lillehei Heart Institute were able to identify a protein, Nkx2-5, which activates a certain gene, and in turn, determines the fate of a group of cells in a developing embryo.

"If we can understand the mechanism, or how certain stem cells choose a particular path, we can alter it to prevent or treat disease," said Daniel Garry, M.D., Ph.D., lead researcher, executive director of the institute, and chief of the cardiovascular division in the Department of Medicine. "This gene discovery provides the key to unlocking the secret of how blood vessels grow."

Researchers knew that certain precursor cells, or progenitor cells, become the three types of cells that make up the cardiovascular system: smooth muscle, endothelial (blood vessel), and cardiac muscle. What they didn't know, until now, is how those progenitor cells end up as one type or another. Garry likened the team's discovery to finding the recipe of how certain cells become blood vessels.

By understanding how the cells develop, Garry said they will be able to study how they might modify the gene to create a desired response.

"Next we are looking at how we could over-express the gene or knock it down," he said.

For example, in the case of heart disease or heart failure, they may be able to "turn on" the gene to make it create new, healthy blood vessels. Or, in the case of cancer, they could turn off the gene to limit blood supply to a tumor, causing it to shrink.

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"Acute drinking increases serotonin release and signaling in brain regions involved in controlling consumption of alcohol," explains study co-author Professor Bankole Johnson, D.Sc., M.D., Ph.D., M.Phil., FRCPsych., chairman of the Department of Psychiatry and Neurobehavioral Sciences in the UVA School of Medicine. "But chronic drinking reduces serotonergic function, leading to a serotonin-deficient state. One hypothesis is that alcoholics drink to alleviate this serotonin-deficient state.

"But it's important to remember that alcoholics differ significantly in their drinking patterns, social backgrounds and disease etiology," says Johnson. "All of these factors may affect both treatment outcomes and medical complications resulting from heavy drinking."

One of the main goals of treatment, Johnson points out, is to reduce the intensity of drinking. "A known genetic marker could be used to sub-type alcoholics and better determine treatment methods that can target specific underlying molecular mechanisms. We hope to determine whether this particular genetic variant can be used as a marker to predict treatment outcomes for different serotonin agents," says Johnson.

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