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.
About VCU and the VCU Medical Center: Located on two downtown campuses in Richmond, Va., Virginia Commonwealth University is ranked nationally by the Carnegie Foundation as a top research institution and enrolls more than 29,000 students in more than 181 certificate, undergraduate, graduate, professional and doctoral programs in the arts, sciences and humanities in 15 schools and one college. Forty of the university's programs are unique in Virginia, and 20 graduate and professional programs have been ranked by U.S. News & World Report as among the best of their kind. MCV Hospitals, clinics and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the leading academic medical centers in the country. For more, see www.vcu.edu.
Journal
Journal of Molecular and Cellular Cardiology