How high glucose levels damage blood vessels

WASHINGTON - Medical College of Georgia researchers have gained fresh insights into how elevated glucose levels, which occur in diabetes, damage blood vessels.

The mechanism can lead to novel strategies for blocking the destruction.

High glucose levels reduce the levels of the powerful vasodilator nitric oxide in blood vessels, a shortfall that increases the risk of high blood pressure and eventual narrows down the vessels.

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

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

“We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons,” said Tostes.

In the study conducted over healthy mice, the researchers found that there was an increased activity by O-GlcNAc in the blood vessels, which competes with another mechanism for modifying proteins called phosphorylation.

In blood vessels, phorphorylation modifies the enzyme that produces nitric oxide, called nitric oxide synthase, so that it makes more of the blood vessel dilator.

O-GlcNAc seems to beat phosphorylation to the punch so there is the opposite result.

The longer O-GlcNAc levels were high, the worse the resulting problem, said Victor Lima, a graduate student at the University of Sao Paulo working with Dr. Tostes.

An animal model of hypertension confirmed the finding that the more O-GlcNAc, the more blood vessels contract because these animals had higher O-GlcNAc levels.

“Now we are trying to see why this is happening and what comes first. Is increased blood pressure leading to changed O-GlcNAc or are augmented levels of O-GlcNAc contributing to the change we see in the vasculature of hypertensives?” said Dr. Tostes.

“If we know how this changes vascular function, we can understand some of the dysfunction that we see in diabetes,” she added.

The study was presented at American Society of Hypertension 24th Annual Scientific Program in San Francisco. (ANI)

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