UF research shows link between roving blood vessel cells, circulatory system damage
Scientists don’t know why cells that normally line blood vessel walls are sometimes found circulating in the blood itself, but a University of Florida study that found abnormally large numbers in kidney disease patients suggests the roving cells might eventually help doctors predict heart and kidney problems.
Blood samples from kidney dialysis patients contained about 50 percent more circulating vessel wall, or endothelial, cells than did samples from healthy people, said nephrologist Mark Segal, M.D., Ph.D., a UF assistant professor of medicine who led the study. And compared with healthy people, patients who were not on dialysis but suffered from diabetes or high blood pressure had over 100 percent more circulating cells.
The findings were published this month in the American Journal of Kidney Diseases.
“Right now, there aren’t good ways to know what someone’s arteries look like, but we know there are lots of different ways that arteries can be injured,” said Segal, with the UF College of Medicine’s division of nephrology, hypertension and renal transplantation. “So it would be nice to have a simple readout to tell us how well the arteries as a whole are doing, and that’s what we hope the circulating endothelial cells will lead us to.”
Endothelial cells form the thin, innermost layer of blood vessel walls, known as the endothelium, which helps regulate blood pressure and the movement of cells and molecules. The average human body contains enough endothelial cells to cover an area about the size of a football field, he said.
Discovered about 30 years ago, circulating endothelial cells are not well understood, Segal said. He believes the number of circulating cells increases when the endothelium is damaged by factors such as stress, high blood pressure, cholesterol and homocysteine, a common amino acid found in red meat.
High blood pressure also is a leading cause of kidney disease, so many dialysis patients suffer from weakened circulatory systems. Each year, about 8 percent of U.S. adult kidney dialysis patients suffer major cardiovascular events such as heart attack or stroke, 10 times the rate for the general public, he said.
Dialysis uses a machine to filter waste products from the blood in patients suffering kidney failure. Almost 400,000 Americans need dialysis to stay alive, according to the National Kidney Foundation.
“Circulating endothelial cells could be a sort of barometer for a patient’s risk for developing vascular diseases,” Segal said. “If you have a patient with high blood pressure it could be very costly to bring down their blood pressure to below 130 over 80. But if we know that person is at high risk of future cardiovascular events or end-organ damage, like kidney failure, then it’s worth the money.
However, if another patient has high blood pressure but is at low risk of future events, then we may only need to bring down their blood pressure to 140 over 90.”
For healthy adults, blood pressure of less than 120 over 80 is considered optimal, according to new guidelines released this year by the National Heart, Lung and Blood Institute.
When damaged, the endothelium produces substances that constrict blood vessels, promote clotting and attract immune system cells, all of which may cause buildup of artery-clogging plaque, a condition known as atherosclerosis or hardening of the arteries. If plaque becomes unstable a clot could form, blocking blood flow to the heart causing a heart attack, or a clot could break off, going to the brain causing a stroke.
In the UF study, Segal and researchers Mehmet Koc, M.D., and Azra Bihorac, M.D., also compared groups of kidney dialysis patients and found those who suffered from atherosclerosis but in whom the disease was well-controlled had the fewest circulating cells. Patients who did not suffer from atherosclerosis had twice as many circulating cells, and patients with uncontrolled atherosclerosis had four times as many.
“That surprised us,” Segal said. “Whether that (data resulted) because the patients with stable atherosclerosis are treated with medication and it lowers their risk is still up in the air.”
In the study, funded by the National Institutes of Health and the UF nephrology division, researchers examined 22 healthy, nonsmoking adults, 29 kidney dialysis patients, 10 people with chronic kidney disease and diabetes, and seven people with chronic kidney disease and high blood pressure. The dialysis patients also were evaluated for any history of cardiovascular disease.
Blood samples from each test subject were chemically treated, then cells were mounted on slides and treated again, and examined under a microscope to identify and count circulating endothelial cells. Finally, the presence of the cells was confirmed with another chemical treatment.
Segal said larger studies could show definitively whether circulating endothelial cells provide an accurate gauge of the endothelium’s condition and whether researchers could use the cells to evaluate therapies designed to improve endothelial health. He said he plans to investigate the interaction between circulating endothelial cells and two types of immune system cells associated with the development of atherosclerosis: monocytes and T cells.
A larger, long-term study might help explain the true effects of circulating endothelial cells on blood vessel walls and on cardiovascular disease, said nephrologist Prabir Roy-Chaudhury, M.D., Ph.D., an associate professor with the University of Cincinnati’s department of internal medicine.
“It’s unclear, in my mind at least, whether circulating endothelial cells are just an indicator of endothelial damage or whether they have some sort of reparative process as well,” Roy-Chaudhury said. “What’s important is that Mark has begun to look at circulating endothelial cells in (this) population of patients.”