Scientists at Bristol University in the UK have identified a kidney disease mechanism that triggers heart attacks and strokes: the mechanism damages the lining of blood vessels, causing them to leak, which in turn raises the risk of circulatory diseases.
Fist author Andy Salmon, Consultant Senior Lecturer in Renal Medicine in the University’s School of Physiology and Pharmacology, and colleagues, write about their findings in the August issue of the Journal of the American Society of Nephrology.
Kidney disease affects about 15% of the UK population. While a small number develop kidney failure, most people with the disease develop circulatory problems and go on to have heart attacks and strokes. These are thought to be due to cellular changes that occur in kidney disease that raise the risk of circulatory diseases by the same amount as smoking.
For their study, Salmon, who is also an MRC Clinician Scientist Fellow, and his team bred rats with a form of chronic kidnely disease that is very similar to that seen in human patients.
These showed the characteristic damage to blood vessel walls as seen in humans. The damage results in leaky blood vessels throughout the body.
The researchers discovered that the damage occurs when the sugar coating that lines the blood vessel walls, called the glycocalyx, is lost.
The glycocalyx is a continuous thick layer of complex sugars and proteins that was only discovered by scientists in the 1960s. It protects the blood vessels from damage.
Damage to the glycocalyx causes blood vessels to become inflamed and leaky. Previous studies have also shown damage to this coating speeds up the process of atherosclerosis, where arteries become “furred up”.
The researchers also found that substances that stick to the inner lining of the blood vessels made them less leaky and work more effectively.
If these same findings are true of human patients, then this could explain the link between chronic kidney disease and the high rate of circulatory disease in humans, conclude the reasearchers.
Salmon told the press:
“These findings are important as it may mean that protecting or even restoring the inner layer could provide protection to blood vessels. There is still much to explore, and while we have shown that damage to the inner layer in kidney disease disrupts the function of some blood vessels, we do not yet know how much it contributes to the final process of “furring up” of arteries.”
He said in previous work they had discovered it was possible to restore the inner lining with growth factors that already exist in the body.
“… but we do not yet have any drugs that achieve the same effect, and so there is much work still to be done,” he added.
Jeremy Pearson, professor and Associate Medical Director of the British Heart Foundation (BHF), told the press:
“We’ve known for some time that there’s a link between kidney disease and heart and circulatory disease but it’s been unclear why. This study may help unravel this mystery and could help lead towards new ways of preventing kidney disease in the future.”
Pearson, who describes the study as a “breakthrough”, also said the finding:
“… brings us closer to understanding how other circulatory diseases develop, including coronary heart disease, the cause of heart attacks. We need to put this vessel sugar coat under the microscope, because it could be important in many different ways.”
Funds from the British Heart Foundation, the Medical Research Council, the Academy of Medical Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases helped pay for the study.
Written by Catharine Paddock PhD