A natural substance secreted by fat cells can protect blood vessels from the damaging effects of inflammation, one of the factors that contribute to heart disease.
Researchers at Jefferson Medical College have shown for the first time in an animal model that the substance , a protein called adiponectin , helps prevent immune system white blood cells from binding to the inside of blood vessel walls. Harnessing adiponectin's properties, the scientists suggest, may someday help protect against the blood vessel damage so prevalent in patients with obesity and diabetes.
Reporting June 1, 2007 in the Journal of Clinical Investigation, researchers led by Barry Goldstein, M.D., Ph.D., professor of medicine and director of the Division of Endocrinology, Diabetes and Metabolic Diseases and Rosario Scalia, M.D., Ph.D., associate professor of molecular physiology and biophysics, both of Jefferson Medical College of Thomas Jefferson University in Philadelphia, discovered that mice lacking adiponectin had an increase in so-called "adhesion" molecules and high levels of white blood cells sticking to the inside of blood vessel walls, which are signs of inflammation. When they gave the animals the "active" piece of the normal adiponectin molecule for 10 days, inflammation in the blood vessels was greatly reduced.
"This is translational work," says Dr. Scalia. "We've used a mouse model to prove Adiponectin conceptually what we see in a test tube system in isolated cells is relevant to an intact physiological system. It's a necessary step before going to humans. These results suggest that perhaps restoring this protein could be important to preventing atherosclerosis and vascular disease."
They used a technique, intravital microscopy, which permits researchers to illuminate blood vessels using fluorescent signals, enabling them to see reductions in white cells on the vessel wall and subsequent lessening in inflammation.
The scientists also looked at the effects of adiponectin on inflammation in normal mice. They gave mice a substance, TNF-alpha, which caused the release of inflammatory substances called cytokines. Injecting the mice with the active adiponectin-fragment reversed the effects of the cytokines and the resulting inflammation.
Inflammation is common in cardiovascular disease. Adiponectin has been shown in cells in culture to block some "adhesion molecules" and receptors that are necessary for white blood cells to interact with the vessel wall, explains Dr. Scalia. "This is the first study to show in animals that this is one of the key mechanisms involved in this protein's anti-inflammatory effect on the vascular system," he notes. "That suggests thinking about either activating the receptors of the target of this protein or administering the fragment."