How red blood cells harm cardiovascular health in diabetes

According to the National Institute of Diabetes and Digestive Kidney Diseases, an estimated 23.1 million people in the United States have type 2 diabetes.

This is a metabolic disease in which the pancreas does not produce enough of the hormone tasked with keeping blood sugar levels in check.

The Centers for Disease Control and Prevention (CDC) note that people with type 2 diabetes face twice the risk of heart disease and stroke, compared with those who are free of diabetes. They are also exposed to cardiovascular risks at an earlier age, say the CDC.

However, the reasons why people with diabetes are more exposed to cardiovascular harm have remained largely unclear, which also means that there is currently no specific preventive treatment.

Now, scientists from the Karolinska Institutet in Stockholm, Sweden, have conducted a series of studies to further investigate the causes of cardiovascular risk in diabetes.

They have revealed that red blood cells undergo certain changes in the case of people with type 2 diabetes, which means that those individuals are more predisposed to heart problems and less well equipped to recover following a cardiovascular event.

These findings now appear in two related papers: the first one published in The Journal of the American College of Cardiology, and the second one in JACC: Basic to Translational Science.

‘Damage to the innermost cell layers’

In the first paper, the authors report that when otherwise healthy blood vessels come into contact with red blood cells taken from people with diabetes, the vessels’ tissue became damaged.

We found that healthy blood vessels exposed to red blood cells from patients with type 2 diabetes suffer damage to their innermost cell layers, the endothelial cells.”

Study co-author Prof. John Pernow

“This phenomenon, which is called endothelial dysfunction, appears early on in the development of diabetes-related vessel injury and greatly reduces the ability of the vessels to dilate while aggravating the inflammation,” Prof. Pernow explains.

In the second published paper, the research team explains how red blood cells affect heart health and predispose individuals to greater harm in the case of a heart attack.

Prof. Pernow and colleagues conducted experiments using red blood cells from mouse models of diabetes, as well as from human patients with this condition. They ascertained that the increased injury occurs due to the abnormal activity of the enzyme arginase.

Findings may lead to preventive therapy

Overactive arginase can impair the production of the free radical nitric oxide, which would normally help blood vessels dilate. It also increased the production of other harmful free radicals within red blood cells.

These findings also allowed the researchers to come up with a solution to address the problem.

“We also found,” says Prof. Pernow, “that treatment that targeted arginase or oxygen-derived free radicals normalised red blood cell function, which meant that their harmful effect on cardiovascular function could be prevented.”

In the future, the team hopes that this will eventually lead to new preventive treatments, which would — as far as possible — eliminate the risk of cardiovascular harm in type 2 diabetes.

“Our hope,” Prof. Pernow adds, “is that this knowledge will give rise to new treatments, specifically targeted at red blood cells, that prevent vascular injury and protect the heart in the event of heart attack in patients with type 2 diabetes.”

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