Hardening of Arteries Is Caused, Not Prevented By The Protein Interferon-gamma, Yale Study Finds

A protein that was previously thought to prevent hardening of the arteries has been shown to actually cause the disease, according to a Yale study.

Interferon-gamma, a key immune factor protein produced by certain white blood cells, was thought to inhibit processes responsible for hardening of the arteries, or arteriosclerosis. But in a study published January 13 in Nature, Yale researchers report that interferon-gamma causes arteriosclerosis in an animal model consisting of different species.

“We’ve found that interferon-gamma causes muscle cells within the artery wall to multiply and form lesions which can obstruct the flow of blood,” said George Tellides, assistant professor of cardiothoracic surgery at Yale School of Medicine. “This observation may improve our ability to develop treatments for arteriosclerosis, which can result in devastating complications such as heart attacks, strokes and gangrene.”

Arteriosclerosis occurs when an increased number of muscle cells within parts of blood vessels contribute to hardening of the arteries. It is considered an immunological disease resulting from the interactions of white blood cells with the cells of the artery wall. The disease occurs most often in individuals with risk factors of smoking, high blood pressure, high cholesterol and diabetes, and may also occur in an accelerated fashion in the transplanted hearts of organ recipients.

In the study, researchers inserted segments of arteries from pig or human hearts into the major blood vessel of mice that lack immune systems. The mice cannot reject the foreign arteries because they are deficient in white blood cells. The mice were then treated with injections of pig or human interferon-gamma for one month, resulting in an abnormal thickening of the transplanted arteries. The arteriosclerotic lesions, consisting of large numbers of muscle cells, occurred in the absence of white blood cells, which, if present, could have confounded the interpretation of the results. Therefore, the results support the idea that arteriosclerosis is an immunological disease, said Tellides.

“From this study, we may identify methods to genetically alter pigs to serve as organ donors of hearts resistant to arteriosclerosis,” said Tellides. “The ‘humanized mouse’ model provides a unique system to test these strategies prior to clinical application.”

The study was part of a novel interdepartmental research program at Yale Medical School, which allows diverse experts, such as heart surgeons and molecular biologists to work together. Collaborators at Yale included Dennis A. Tereb, Nancy C. Kirkles-Smith, Richard W. Kim, Jean H. Wilson, Jeffrey S. Schechner, Marc I. Lorber and Jordan S. Pober.

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326