Researchers at the Karolinska Institute and Karolinska University Hospital in Sweden have shown that arginase might play a significant role in the development of cardiovascular disease in patients who have type 2 diabetes. According to the scientists, who just published their results in Circulation, arginase prevents the formation of protective nitrogen oxide in the blood vessels, and treatments that inhibit arginase reduce the risk of angina in diabetics.
“The fact that we could demonstrate the presence of arginase in several types of cell in the vessel wall gives us an entirely new explanatory model for the development of complications in these patients,” explained lead investigator John Pernow, M.D., Ph.D.
Complications in diabetes patients result from constrictions of the blood vessels caused by atherosclerosis. The ensuing reduction in blood flow and oxygen supply can lead to angina, myocardial infarction or stroke, and possible amputation. Atherosclerosis is more common in people who smoke and who have high levels of blood lipids, although the risk is most pronounced in patients with diabetes. The reason for this correlation between diabetes and cardiovascular disease has largely eluded scientists and there is still no specific treatment for these complications.
In this current study, the researchers analyzed the function of arginase in the blood vessels of patients with both type II diabetes and angina and found that it prevents the formation of nitric oxide in the vessel wall. After introducing nor-NOHA, which is known to inhibit arginase, they observed a significant improvement in blood vessel function in these patients. A comparative analysis showed that the arginase inhibitor did not have the same positive effect on patients with angina but without type II diabetes, and had no effect at all on healthy controls.
“Nitric oxide has a very important function to perform in the vessel walls,” says Professor Pernow. “Apart from dilating them, it prevents the formation of plaque. For some reason, however, the mechanism is impaired in people with diabetes.”
A total of 48 patients were included in the study and the team is now planning a larger follow-up study to confirm their results and develop treatments using arginase inhibitors.
According to the U.S. Department of Health and Human Services, diabetes affects 25.8 million people of all ages (approximately 8.3% of the U.S. population). The International Diabetes Foundation estimates that the number of adults with diabetes in Europe totals 55.2 million, accounting for 8.5% of the adult population. National prevalence rates for diabetes show a wide variation from 2.1% in Iceland to 12.0% in Germany.