Scientists get $9.3 million to study diabetes link with heart disease

By Catherine Seigerman Wolz

People with diabetes are four times as likely to develop heart disease, which accounts for three quarters of deaths of diabetics, but researchers have not yet proven why. As the number of diabetic Americans soars past the current estimate of 16 million, according to the American Diabetes Association, scientists are looking at the link between both diseases, starting at the cell level.

One of the largest such efforts has begun this month at the U.Va. Health System with a five-year, $9.3 million grant from the National Heart, Lung and Blood Institute at the National Institutes of Health.

Dr. Jerry L. Nadler, Kenneth R. Crispell Professor of Internal Medicine and chief of the Division of Endocrinology and Metabolism, and researchers from the U.Va. Heart Center and Department of Bioengineering will investigate why diabetics have higher incidence and death rates from heart disease, mainly atherosclerosis or hardening of the arteries, as well as lower recovery rates from procedures such as angioplasty.

“The goal of the study is ultimately to develop new medications or gene therapy approaches to prevent heart disease due to diabetes,” Nadler said.

The study will focus on a gene called 12-lipoxygenase (12-LO), an enzyme that generates inflammatory molecules. When cells are exposed to high levels of sugar or insulin in the blood, as occurs in people with diabetes, 12-LO produces inflammatory molecules that can damage the blood vessels and lead to atherosclerosis.

“We believe 12-LO is one key enzyme causing the heart complications related to diabetes, and no one has yet found a way to block it with any known medications,” Nadler said.

To test the role of this enzyme, U.Va. researchers developed a ribozyme that acts like “molecular scissors” and can be targeted to disable the 12-LO gene. The researchers can then find out if blocking 12-LO will protect the blood cells from damage and destruction.

“I am very excited about this study because it shows the close relationship between endocrinology and cardiology, and that clinicians in these two fields can work together with outstanding basic science researchers. At the University, resources in all of three of these fields are excellent,” Nadler said.