New Molecular Trigger Described for Hypertension, Diabetes

By Ed Edelson
HealthDay Reporter
Tuesday, July 1, 2008; 3:00 AM

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MONDAY, June 30 (HealthDay News) -- A newly discovered molecular malfunction may explain the development of high blood pressure, diabetes and immune problems, researchers report.

Rogue versions of enzymes known as proteases roam the body, clipping off working segments of the receptors that allow insulin to enter cells and do its job, according to a report in the June 30 online issue of Hypertension.

That uncontrolled enzymatic activity also reduces the immune system's response to infection and raises blood pressure, the report noted.

"We are describing a new mechanism for disease and injury to the body," said study author Frank DeLano, a research scientist with the department of bioengineering at the University of California, San Diego. "It is an idea that hasn't been presented before. If we apply a protease inhibitor, we can prevent the damage we see in laboratory animals."

DeLano and his collaborator, Geert Schmid-Schonbein, a professor of bioengineering at UCSD, have been working with a widely used laboratory model of disease, a rat bred to have high blood pressure.

They have found that proteases, whose function is to clear away molecular debris, can go awry and split apart a number of different cell wall receptors. If insulin receptors are damaged, normal metabolism of glucose is not possible, and diabetes can be the result. Proteases can also damage receptors that are vital for the functioning of infection-fighting leukocytes.

The researchers also found that protein receptors on the surface of cells are clipped off as the rats develop high blood pressure. "Many receptors in blood vessels cause them to relax," DeLano said. "Many proteases we see in the animals cleave receptors responsible for relaxation." Giving the rats doxycycline, an antibiotic that is also a protease inhibitor, brought down their blood pressure and restored normal immune system function.

The proteases that cause the damage leak out of the intestine, DeLano said. "The mechanism is a leaky or permeable intestine," he said. "We call it leaky gut syndrome."