JDRF Research
Researchers Find Cause for Blood Vessel Damage in People With Diabetes
JDRF-funded researchers at the University of Florida have made a potentially major discovery about why blood vessels in people with diabetes become damaged. They found that primitive repair cells that normally mend the damaged lining of blood vessels become too rigid to move in people with diabetes, leading to heart disease and complications that harm the eyes, kidneys, and nerves. Just as important, a simple laboratory procedure might be able to undo the damage, according to a study in the scientific journal Diabetes.
“These research findings present a new mechanism underlying the development of diabetic microvascular complications, showing that the damage caused by defects in blood vessel repair is potentially reversible,” said Antony Horton Ph.D., JDRF’s Program Director for Diabetes Complications. “The finding holds great importance for understanding and treating a broad range of diabetic complications.”
The Florida researchers, led by Mark Segal, Ph.D., showed they can restore the repair cells’ flexibility by dosing them with nitric oxide, a signaling molecule that occurs naturally in blood. Scientists have observed that people with diabetes have low levels of nitric oxide, so their primitive repair cells, called endothelial progenitor cells (EPCs), may have become too rigid to migrate to restore the damaged endothelial layer lining the blood vessels. The repair cells, made in the bone marrow, normally travel throughout the body to sites where blood vessels need mending and are drawn to those spots by signals from a protein called SDF-1.
The researchers isolated EPCs from blood samples drawn from patients with diabetes. They found that the cells were rigid and unable to move properly in response to SDF-1 signals. When the cells were exposed to nitric oxide, they became more supple, and their ability to move improved dramatically. The scientists found that nitric oxide affects the cytoskeleton, or scaffold, of the cell, and that by adding nitric oxide, they were able to rearrange the scaffold.
Dr. Segal said that many drugs already on the market have been shown to affect nitric oxide levels within EPCs. This suggests that medications could be effective at restoring EPC mobility and thus help to block vascular complications. He said that there might be ways to harvest EPCs from a patient, treat them with nitric oxide outside the body and then return them to the patient, where they would perform capably.