Enzyme Linked to Angina in Patients with Diabetes

New research shows that arginase may contribute to angina in patients with type 2 diabetes. Suppressing the enzyme may help improve blood flow.

Researchers at Karolinska Institutet and Karolinska University Hospital have shown that the enzyme arginase may have “a key part to play in the development of cardiovascular disease in patients who already have type II diabetes.” Arginase prevents the formation of protective nitrogen oxide in the blood vessels, and inhibiting this enzyme may reduce the risk of angina in patients with diabetes.

The researchers published their results in Circulation in an article titled “Arginase Inhibition Improves Endothelial Function in Patients with Coronary Artery Disease and Type 2 Diabetes.”

In the study, the researchers assessed forearm endothelium-dependent (EDV) and endothelium-independent (EIDV) vasodilatation via venous occlusion plethysmography at baseline and during intra-arterial infusion of an arginase inhibitor in a cohort of 16 patients with coronary artery disease (CAD), 16 patients with CAD and type 2 diabetes, and 16 age-matched healthy control subjects. They also co-infused a nitric oxide synthase inhibitor.

The authors measured expression of arginase in the internal mammary artery of patients who were undergoing bypass surgery. They found that arginase inhibitor was associated with a marked increase (nearly double) in patients with CAD and CAD + diabetes. The nitric oxide synthase inhibitor “completely inhibited the increase in EDV” induced by the arginase inhibitor. They also found that “EIDV was slightly improved” by arginase inhibitor in patients with CAD + diabetes. According to the authors “arginase I was expressed in vascular smooth muscle cells and endothelial cells, and arginase II was expressed in endothelial cells of patients with and without diabetes.”

These findings indicate that arginase inhibition “markedly improves endothelial function in patients with CAD and type 2 diabetes suggesting that increased arginase activity is a key factor in the development of endothelial dysfunction.”

According to a release from the Karolinska Institutet, “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.”

Lead investigator John Pernow, MD, FESC, said that “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.” He also noted that “Nitric oxide has a very important function to perform in the vessel walls. Apart from dilating them, it prevents the formation of plaque. For some reason, however, the mechanism is impaired in people with diabetes.”