In the September issue of Journal of Clinical Investigation, the Penn researchers suggest novel genetic causes for and new therapeutic agents against cardiac hypertrophy and heart failure. Furthermore, the researchers demonstrate that anti-HDAC drugs can block the development of hypertrophy in animal models.
"In our studies, we determined that valproic acid, an HDAC inhibitor used to treat seizure disorders, is effective in preventing heart muscle cells from enlarging," said Jonathan A. Epstein, MD, Associate Professor in the division of Cardiovascular Medicine within Penn's Department of Medicine. "In recent years, drug companies have also begun developing more advanced HDAC inhibitors to treat cancer. These HDAC inhibitors may be among the first known medications to prevent cardiac hypertrophy."
Cardiac hypertrophy can be a healthy physiological response to events, such as aerobic exercise, where heart cells grow larger like any other well-conditioned muscle. Pathological hypertrophy, however, may result from genetic mutation or, most commonly, from the consequences of an unhealthy cardiovascular system.
"The exertion of pushing blood against high resistance in the setting of high blood pressure or overcompensation for heart muscle lost during a heart attack can cause heart muscle
cells to enlarge," said Epstein. "While it might be helpful at first, hypertrophy can increase the stress placed on the heart and begin a downward spiral of events that ultimately leads
Contact: Greg Lester
University of Pennsylvania School of Medicine