University of Virginia Health System

U.VA. INVESTIGATORS RECEIVE $9.3 MILLION TO STUDY DIABETES LINK WITH HEART DISEASE

People with diabetes are four times as likely to develop heart disease -- but researchers have not yet proven why. Heart disease continues to account for almost three quarters of the deaths in people with diabetes, studies show. As the number of diabetic Americans continues to soar 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 to date has begun this month at the University of Virginia Health System with a $9,314,306 grant to span five years 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, is principal investigator for the program project grant. The July 23 issue of U.S. News and World Report ranked U.Va.'s Division of Endocrinology and Metabolism sixth best of all hospitals nationwide.

Nadler and researchers from the U.Va. Heart Center and Department of Bioengineering will investigate why people with diabetes 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 and coronary stents.

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

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. If 12-LO gets overly activated, damage to endothelial cells or excessive growth of smooth muscle cells in the blood vessel can occur and lead to heart disease.

To test the role of this enzyme, U.Va. researchers developed a ribozyme, or molecular scissors, that 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.

The study will use a pig model specially developed to simulate heart disease in the diabetic patient. A pig's blood vessels are similar to a human's. NIH sees the pig model as an important new tool that U.Va. can share with other research institutions around the world to expedite research into diabetes and heart disease, Nadler said. Specialized mouse models already developed by U.Va.'s Diabetes Center and Department of Bioengineering also will be used.

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 of Virginia, resources in all of three of these fields are excellent, Nadler said.

August 10, 2001