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Groundbreaking model of heart disease rewarded with NIH Pioneer Award
Date:9/23/2009

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An estimated 3 million Americans suffer from heart failure, with 500,000 new cases diagnosed annually. Disease that leads to heart failure long has been associated with oxidative stress, the process in which the body produces "free radical" molecules in response to oxygen intake. Once they're produced, free radicals roam the body, creating chemical reactions that damage organs and other tissue.

To protect cells from free radicals, the body makes antioxidants. Benjamin's work focuses on a particular antioxidant, reduced glutathione, which is produced when a protein called alpha B-Crystallin unfolds inside of cells. When mutated versions of the human gene that makes alpha B-Crystallin were placed in mice, however, certain metabolic pathways were improperly activated, which led to excessive production of reduced glutathione and heart damage in the animals. Benjamin terms this condition "reductive stress."

Until recently, reductive stress hasn't been looked at in the context of disease. But Benjamin showed that mice with too much reduced glutathione had increased heart failure rates, while those with normal levels of the antioxidant did not develop heart failure. Given the role of antioxidants, the theory is counterintuitive, Benjamin acknowledges. But if he's correct, it could lead to developing an entirely new class of "antireductant" drugs to treat or even prevent heart disease caused by reductive stress. "Our findings show that the potential for reductive stress causing heart disease definitely warrants more investigation," Benjamin says. "The Pioneer Award will enable us the freedom to investigate the consequences and mechanisms of reductive stress and, hopefully, do the kind of work that can be transformative."

Benjamin's research represents the kind of imaginative and searching science that the U of U values in its faculty, according to Lorris Betz, M.D., Ph.D., University of Utah senior vice president for health scie
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Contact: Phil Sahm
phil.sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

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