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 to move 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 issue of the journal Diabetes.
Having diabetes markedly raises the risk of developing a host of other ailments, from heart disease to stroke, blindness and kidney failure. Many arise after blood vessels suffer damage, spurring the accumulation of fatty deposits in the arteries or the wild, blinding growth of capillaries in the eye.
"We're interested in what happens in the body at the molecular level to cause these life-threatening problems," said Mark S. Segal, Ph.D., an assistant professor of nephrology, hypertension and transplantation at University of Florida College of Medicine. "Our work is focused on understanding why diabetic patients are at increased risk for these other diseases."
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 they fail to report for duty.
"Part of the defect we think is occurring in diabetic patients is these cells do not carry out appropriate repair, and therefore these patients are at higher risk for cardiovascular disease and other complications," Segal said.
The inability of the cells to repair the peripheral vasculature, the large 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 it 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."
UF 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 when nitric oxide gas was added, Segal said, the cells lost their rigidity, becoming suppler, 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 the 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."
UF scientists suspect that in the 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 healthy people. That causes the cell to stiffen.
The finding raises the possibility that nitric oxide could someday be used to keep the cells mobile, enabling them to travel to distant sites when needed, Segal said.