Abnormal fat metabolism underlies heart problems in diabeti...(a key to identifying cardiolipin decreas...)

Date:8/13/2007

a key to identifying cardiolipin decrease in diabetic hearts. Children born with Barth syndrome have weak hearts and often die young from heart failure. These children have mutations that prevent cells from producing enough cardiolipin. The connection between cardiolipin and heart disease in Barth syndrome led the Washington University researchers to wonder if cardiolipin was also affected in diabetic hearts.

But in order to measure cardiolipin, the researchers needed a way to distinguish it from the numerous other lipids found in heart cells. Fortunately, Gross and his colleagues have been developing and refining a highly sophisticated set of techniques that allow them to separate and quantify thousands of different lipids based on their subtle structural differences. The set of techniques has been termed "shotgun lipidomics" because they very rapidly determine which lipids are in tissues and blood.

"Shotgun lipidomics provide a precise way to measure changes in heart lipid content," says first author Xianlin Han, Ph.D., assistant professor of medicine. "We found a dramatic depletion of cardiolipin in heart muscle as early as five days after diabetes was induced in mice."

"These results suggest that cardiolipin alterations underlie heart dysfunction in diabetic heart disease and may be a useful biomarker for diagnosing cardiovascular disease in diabetes," Gross says. "Measuring alterations may be a way to tell the severity of heart disease and to evaluate how well therapies work. In addition, these findings suggest potential new therapeutic approaches."

Even though the research team found a depletion of an important type of lipid in diabetic heart tissue, diabetic heart muscle cells actually take in excess lipids. But as these lipids enter cells they activate lipid-digesting enzymes. In previous studies, Gross and colleagues identified a particular lipid-digesting enzyme that becomes more active in diabetic heart muscle and contributes to the
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Contact: Gwen Ericson 314-286-0141 Washington University School of Medicine Source:Eurekalert

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