Heart failure, progressive and potentially fatal weakening of the heart muscle, is associated with both obesity and diabetes, but the mechanisms by which damage occurs are not well-understood, said senior author Heinrich Taegtmeyer, M.D., Ph.D., professor of cardiology.
"In cardiology, we've long been concerned about fat accumulating in the artery walls and blocking the flow of blood to the heart. What we are finding now is that the buildup of fat doesn't stop in the blood vessels, it's actually worse in heart muscle cells," Taegtmeyer said. "We also report in this paper that diabetes and obesity appear to cause metabolic irregularities in the heart tissue."
Gene expression and protein findings in the paper provide potential long-term targets for treating heart failure, which afflicts 5 million U.S. patients annually.
Researchers examined 27 failing hearts that were removed during transplants and compared them to eight donor hearts that were not failing but were otherwise unsuitable for transplant.
Eight of the failing hearts (30 percent) showed high levels of triglycerides a fat storage and transport molecule. Levels of triglycerides in failing hearts were four times the level in obese or diabetic patients as they were in non-failing hearts.
The research team associated this buildup of triglycerides in the heart muscle, called lipotoxicity, with dysfunctional expression of genes related to the heart's metabolism of fatty acids, its contractile function, and an inflammatory protein known to contribute to insulin resistance.
The human results track with a rat model of the
Contact: Scott Merville
University of Texas Health Science Center at Houston