Fat Cells Surrounding the Coronary Arteries May Play a Central Role in Heart Disease

"The fat cells surrounding coronary arteries may ultimately prove to be an important link between obesity, type II diabetes, and coronary artery disease..."

The fat cells surrounding coronary arteries may play a central and previously unrecognized role in the development of cardiovascular disease, according to a study by University of Iowa researchers. [1] Researchers led by Neil Weintraub, MD, Professor of Medicine, Department of Medicine, Division of Cardiology, University of Iowa,* has shown that the perivascular adipose tissue that envelops most large blood vessels in humans is involved in promoting coronary artery inflammation and growth of vasa vasorum and collateral coronary vessels in response to ischemia.

The team's findings were presented by associate research scientist Lynn Stoll, PhD, on April 4 at Experimental Biology 2006, the meeting of the Federation of American Societies for Experimental Biology (FASEB), held in San Francisco, California. Her presentation was part of the scientific program of the American Society of Investigative Pathology.

There is growing evidence that adipocytes from different corporeal fat depots have distinct functional properties. Once thought of as mere energy storage depots, 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. Epicardial adipocytes have been shown to produce inflammatory mediators, and the Iowa researchers hypothesized that these cells might have a direct role in the pathogenesis of the atherosclerosis. Their investigation was the first to study the functional properties of isolated epicardial adipocytes.

The research team isolated and cultured epicardial adipocytes from freshly harvested postmortem hearts and, for comparison, subcutaneous and perirenal adipocytes from the same donors. They found that:

Compared with adipocyte precursor cells (pre-adipocytes), epicardial adipocytes were associated with much higher levels of adipokine and pro-inflammatory cytokine expression, especially the pro-inflammatory mediator CD14, which was expressed at 50-fold higher levels compared with pre-adipocytes.

Epicardial adipocytes showed substantial cyclo-oxygenase (COX) and epoxide hydrolase activity. The major COX metabolite, prostaglandin E 2 (PGE 2), plays an important role in angiogenesis and inflammation. Epoxide hydrolase plays an important role in endothelial function.

Exposure to hypoxia caused increased expression of vascular endothelial growth factor (VEGF), a peptide that stimulates angiogenesis, in both epicardial adipose tissue explants and cultured epicardial adipocytes.


Conditioned medium from epicardial adipocytes (but not control medium or medium from epicardial pre-adipocytes or subcutaneous adipocytes) strongly promoted growth and tubule formation by human coronary artery endothelial cells (angiogenesis). "
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