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Nitric Oxide Holds Promise for Diabetes Cell Repair

University of Florida researchers say primitive cells that act like molecular maintenance men—traveling throughout the body to repair damaged blood vessels—become too rigid in patients with diabetes, fueling the disease’s vascular complications. But they have found a way to restore the cells’ flexibility, at least in the laboratory, according to findings published in the January 2006 issue of the journal Diabetes.

Many complications of diabetes, such as heart disease, stroke, blindness, and kidney failure, arise after blood vessels suffer damage, spurring the accumulation of fatty deposits in the arteries, or an overgrowth of new capillaries in the eye.

“We’re interested in what happens in the body at the molecular level to cause these life-threatening problems,” says Mark S. Segal, PhD, an assistant professor of nephrology, hypertension, and transplantation at UF’s College of Medicine. “Our work is focused on understanding why diabetic patients are at increased risk for these other diseases.”

CELLS FAIL TO REPAIR

The problem is rooted in the body’s response to vascular injury. The bone marrow churns out cells crucial to repairing the damaged lining of blood vessels. But sometimes these cells fail to report for duty.

“Part of the defect we think is occurring in diabetic patients is that these cells do not carry out appropriate repair,” Segal said.

The inability of these cells to repair the large blood vessels of the body is similar to their inability to repair the small vessels within the eye, he added.

“In the vasculature, it leads to atherosclerosis, and within the eye, the same process leads to diabetic retinopathy,” he said. “So the link is we have one defect in these cells that can lead to both of these problems.”

NITRIC OXIDE IS KEY

University of Florida researchers isolated these repair cells from blood samples drawn from patients with diabetes and chronic kidney disease, and studied them in the laboratory. The cells were unable to move about normally. But, after nitric oxide gas was added, Segal reported, the cells lost their rigidity, becoming more supple, and their ability to move dramatically improved.

In the body, nitric oxide occurs naturally. It helps the repair cells move out of the bone marrow where they are made, and it opens blood vessels and improves the uptake of oxygen. Patients with diabetes, however, commonly have low levels of nitric oxide.

“We went on to show that actually what’s happening is nitric oxide is affecting the skeleton, or scaffold of the cell, and, by adding nitric oxide, we’re able to rearrange that scaffold,” Segal said. “When we rearrange the scaffold, the cells are able to migrate. The benefit of this is that when cells have improved movement, they are able to repair the endothelium (the lining of the blood vessels) better, and perhaps prevent atherosclerosis.”

University of Florida scientists suspect that in cells taken from diabetic patients, nitric oxide interacts with a protein that steers the protein to the cell surface instead of inserting it into the cell, as it would in nondiabetic people. That process causes the cell to stiffen.

FUTURE TREATMENT POSSIBILITIES

The finding raises the possibility that nitric oxide could someday be used to keep the cells mobile, enabling them to travel to distant sites as needed, Segal said.

“The importance of this is related to other work that has shown that many drugs being used on the market today actually affect nitric oxide levels within these cells,” Segal said. “So, someday, there may be two ways to help people whose cells may not function as well as they should. One is through certain medications—there may be a way we could actually give medications that would affect the nitric oxide level within these cells and enhance their migratory ability. The other is through certain instances where we might actually collect these cells, treat them with nitric oxide outside the body, and give them back to the patient, to help improve the cells’ migration ability.”

In the future, for example, patients with diabetes and atherosclerosis who require angioplasty might receive injections of their own repair cells. The cells would have been removed, incubated with nitric oxide to improve their function, and returned. They would theoretically help blood vessels heal more quickly, and perhaps keep new fatty deposits from forming.

For more information, contact the University of Florida, office of the Senior Vice President for Health Affairs, PO Box 100253, Gainesville, FL 32610-0253; telephone: (352) 273-5810; Web site: www.news.health.ufl.edu.