New study shows antibiotic may protect the heart

RICHMOND, Va. (July 5, 2006) – Virginia Commonwealth University researchers studying rapamycin, an antibiotic used to boost organ survival in transplant patients, have found that the drug may protect the heart against tissue damage following acute heart attack.

In the July issue of the Journal of Molecular and Cellular Cardiology, the official publication of the International Society for Heart Research, researchers demonstrated for the first time that pretreatment with a clinically relevant dose of rapamycin induces a protective effect against heart attack injury and reduces programmed cell death.

Researchers believe through the opening of the mitochondrial KATP channel of heart cells, rapamycin enables cells to maintain ATP levels. Mitochondria are cellular organelles critical for converting oxygen into ATP, the key fuel for cellular function.

"Rapamycin may one day be beneficial as a potential therapeutic strategy to limit cell death caused by ischemia or reperfusion injury, and possibly long-term prevention of ventricular remodeling – the changes in size, shape and function that may occur to the left ventricle of the heart," said Rakesh C. Kukreja, Ph.D., professor of medicine and Eric Lipman Chair of Cardiology at VCU. Kukreja is lead author of the study.

Rapamycin blocks protein synthesis by inhibiting the mammalian target of rapamycin (mTOR), an essential component in the pathway of the cell cycle progression. The drug has been found to be important in transplant medicine and especially in kidney or heart transplantation. Additionally, Kukreja said that because of the antibiotic's antigrowth properties, rapamycin effectively reduces coronary restonosis, the abnormal narrowing of a blood vessel. In coronary angioplasty, stents coated with rapamycin are implanted to reduce the risk of restonosis.

"A significant clinical question will be whether or not rapamycin coated stents can be utilized in patients to favorably affect damaged heart muscle beyond the blockage causing a heart attack," said George W. Vetrovec, M.D., chair of cardiology at VCU's School of Medicine, and co-author of the study.

For the last several years, Kukreja and his colleagues have studied a class of erectile dysfunction drug known as phosphodiesterase-5 inhibitors as part of ongoing research into heart protection. The team first investigated Viagra®, generically known as sildenafil, and more recently, Levitra®, generically known as vardenafil, and found that both compounds showed protective effects in the heart during experimental heart attacks in animal models.

This work was supported by grants from the National Institutes of Health, and American Heart Association, National Center.

Kukreja and Vetrovec collaborated with VCU researchers, Shakil A. Khan, M.D., Fadi N. Salloum, Ph.D., Anindita Das, Ph.D., Lei Xi, M.D.

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About VCU and VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.