Wednesday, July 5, 2006
(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.
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.
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
"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
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
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 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.