Mouse Study Finds Anticancer Drug Prevents Cardiac Hypertrophy

Studies in mice suggest that an experimental cancer drug acts to block the development of cardiac hypertrophy and may be of use in preventing or reversing the damage to the heart caused by chronic high blood pressure.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA; www.utsouthwestern.edu) had discovered previously that HDAC (histone deacetylase) inhibitors prevented disease-associated heart growth. To further this research they genetically engineered a line of mice that overexpressed the proautophagy protein Beclin 1 in cardiomyocytes. These mice displayed overactive autophagy that induced hypertrophy leading to heart failure.

The investigators reported in the March 8, 2011, issue of the journal Proceedings of the [US] National Academy of Sciences that treating the genetically engineered mice with the HDAC inhibitor trichostatin caused ventricular mass to revert to near-normal levels and ventricular function to normalize completely.

"The heart decreased back to near its normal size, and heart function that had previously been declining went back to normal," said senior author Dr. Joseph Hill, professor of cardiology at the University of Texas Southwestern Medical Center. "That is a powerful observation where disease regression, not just disease prevention, was seen. This opens the way for a new therapeutic strategy in hypertensive heart disease, one we can test for potential to promote regression of heart disease."

"This is one of those exciting, but rare, examples where an important finding made originally in yeast moved into mouse models and is soon moving to humans," said Dr. Hill. "That is the Holy Grail for a physician-scientist – to translate those sorts of fundamental molecular discoveries through preclinical studies and ultimately in humans."

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University of Texas Southwestern Medical Center