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Arginase inhibitors might prevent diabetic heart disease

Kathleen Blanchard's picture
Blocking an enzyme could help reduce the chances of heart disease for diabetics.

Researchers may have discovered why diabetes leads to heart disease, despite intensive lifestyle interventions. Scientists from the Karolinska Institutet and Karolinska University Hospital have found a key enzyme known as arginase could be responsible for plaque formation and artery constriction that leads to angina for type 2 diabetics.

Arginase blocks nitric oxide (NO) that is naturally produced in the body and essential for keeping blood vessels relaxed. Diabetes complications occur when blood vessels become constricted from plaque formation or atherosclerosis.

Recently, researchers found even with interventions like weight loss, medications and exercise, heart disease risk remained high for people living with the disease.

The trial, called the Look AHEAD study was stopped because researchers failed to find ways to prevent cardiovascular problems in diabetics through intensive lifestyle interventions, making arginase an important new focus.

Heart disease is a leading source of death and disability associated with diabetes. According to the National Diabetes Information Clearinghouse (NIDC), adults with diabetes are 2 to 4 times more likely to develop heart disease than non-diabetics.

A 2009 study from Georgia Health Scientists pinpointed elevated arginase levels as a cause of diabetic eye disease or retinopathy that can lead to blindness.

Dr. Wenbo Zhang, the paper's first author said in a press release regarding the study, “…understanding just how arginase regulates inflammation should lead to new therapies for many acute and chronic inflammatory diseases in the eyes and other organs.” The finding was published in the American Journal of Pathology.

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Similarly, Penn State scientists discovered arginase also plays a role in diabetic kidney disease, in findings published last year.

Lead investigator Professor John Pernow said in a media release regarding the newest finding, “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."

Lower NO levels in the body makes blood vessels ‘sticky’ and more prone to develop blockage from white blood cells that accumulate inside arteries and small blood vessels (microvascular disease) to cause a variety of cardiovascular problems like angina, peripheral vascular disease and diabetic retinopathy.

For the current study, researchers first confirmed the presence of arginase in patients with type 2 diabetes and angina, confirming the enzyme blocks nitric oxide.

When the researchers gave patients with type 2 diabetes and angina a known arginase inhibitor they noted a significant improvement in blood vessel functioning. The treatment had no effect on healthy participants used as controls, or on patients with angina who were not diabetic. The study included 48 people.

The researchers are planning larger trials in hopes of developing new diabetes treatments. Arginase inhibitors might help prevent a variety of diabetes complications. The presence of the enzyme that blocks nitric oxide to lead to constricted blood vessels could explain why diabetes is a leading cause of stroke and heart attack.

Karolinska Institutet
November 27, 2012

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