Dr. Lynn Stoll presented the research team's findings on April 4 at Experimental Biology 2006 in San Francisco. Her presentation was part of the scientific program of the American Society of Investigative Pathology.
Once thought of as mere storage depots for excess energy, fat cells ("adipocytes") are now known to be highly active metabolically, releasing potent pro-inflammatory proteins and hormones that regulate inflammation, blood pressure, insulin activity, and other biological processes. Where fat cells are located has a major influence on their impact, as seen in the fact that visceral fat surrounding the internal organs ("apple" body shape) is far more highly correlated with development of diabetes and cardiovascular disease than subcutaneous fat in the thighs and buttocks (pear" body shape).
One area of adipose tissue that has received little attention is the perivascular adipose tissue that envelops most large blood vessels in humans. The function of these fat cells is largely unknown, but the fact that the coronary arteries are embedded in fat tissue led the Iowa researchers to believe that these fat cells have a direct role in the pathogenesis of the atherosclerosis to which these arteries are so highly susceptible.
The research team, led by Dr. Stoll and senior investigator Dr. Neal Weintraub, isolated and cultured adipocytes from the fat tissue surrounding human coronary arteries and, for comparison, cells from other fat tissue including subcutaneous fat. Their experiments showed three important differences in how the fat cells from around the coronary arteries (the epicardial adipocytes) function compared to fat from other areas of the body:
- The epicardial adipocytes release greater amounts of harmful, inflammation-producing cytokines in response to certain stimuli.
- Epicardial adipocytes (but not adipocytes from subcutaneous or renal fat) strongly induce coronary artery endothelial cells to form elongated, branching structures indicative of blood vessel formation (angiogenesis).
- When exposed to hypoxia, epicardial adipocytes produce larger amounts of vascular endothelial growth factor (VEGF), a peptide that stimulates angiogenesis.
Since epicardial fat tissue receives its blood supply directly from the adjacent coronary artery through the vasa vasorum, a network of tiny blood vessels near the outer surface of the heart, the Iowa team's results suggest that coronary artery blockages may lead to oxygen deprivation (ischemia) in the surrounding adipose tissue, which could contribute locally to vascular inflammation. At the same time, epicardial adipocytes could act as a sensor for local ischemia, serving as a powerful stimulator of angiogenesis and resulting in proliferation of the vasa vasorum, which has been suggested to contribute to coronary artery disease by causing intraplaque hemorrhage and accumulation of cholesterol from red blood cell membranes.
The fat cells surrounding coronary arteries may ultimately prove to be an important link between obesity, type II diabetes, and coronary artery disease, all of which are increasing at epidemic rates in the U.S. and throughout the world, says Dr. Stoll. A better understanding of how epicardial adipocytes sense and respond to inflammation and ischemia could lead to new, rationally designed therapies for heart disease.
Other members of the research team participating in these ongoing studies of epicardial adipose tissue and vascular inflammation include Sara Romig-Martin, Allan Harrelson, Eric Dickson, Gerene Denning, Xiang Fang, Arthur Spector, Salam Sbaity, Bryon Johnson, and Satjit Adlakha.
These studies are funded by the National institutes of Health and the Veterans Affairs Office of Research Support, along with a grant from Pfizer.