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Can Diabetic Damage To Blood Vessels Be Blocked?

Posted May 13 2009 11:33pm
Medical College of Georgia researchers propose that diabetes-induced damage to blood vessels may, someday, be minimized by drugs developed based on new knowledge of how the damage occurs.

They found a decreased ability of blood vessels to relax resulted from increased activity of a natural mechanism for altering protein form and function, says Dr. Rita C.Tostes, physiologist in the MCG School of Medicine.

The researchers suspect increased modification of proteins by a glucose-derived molecule is a player in vascular problems associated with hypertension, stroke and obesity as well.

Elevated glucose levels tend to reduce nitric acid levels in the bloodstream. Nitric acid is a powerful vasodilator and reduced levels may promote constriction of blood vessels, thereby raising blood pressure. Unfortunately, about 75% of diabetics die as a result of some form of cardiovascular disease (heart or blood-vessel related).

"We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons," Dr. Tostes says.

A small percentage of the glucose in the body is converted to O-GlcNAc and this can modify proteins. Mouse research demonstrates that O-GlcNAc competes with the primary mechanism that produces nitric acid in the blood vessel, thereby causing a tendency for blood vessel constriction instead of dilation. The more glucose available ... the more O-GlcNAc there is to compete with that primary mechanism.

To make sure they were targeting the O-GlcNAc sugar and not dealing with other effects of glucose on blood vessels, the researchers blocked the enzyme OGA, an enzyme that normally removes O-GlcNAc from proteins so they can revert to their normal state.

If the findings continue to hold true, drugs similar to those they use in the lab to inhibit OGA or OGT, the enzyme that adds O-GlcNAc to the protein, could one day help reduce the significant cardiovascular risk associated with diabetes, Mr. Lima says. "I think it looks very promising," Dr. Tostes adds.

Future studies will include blocking the pathway for adding O-GlcNAc in hypertensive animals to study the impact on blood pressure and vascular function.

The complete, and fairly scientific, Science Daily article can be seen
here.

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