UCSF cardiology chief builds a case for two new targets for heart drugs

Following up on some promising rodent studies, a team of investigators at UC San Francisco has helped substantiate that elevated levels of two proteins are linked with healthier hearts--an insight that will likely inspire more work into new cardiology therapies.

Building on a pair of mouse studies at Harvard published in 2013 in Cell and in 2014 in Science, the researchers tracked the outcomes of 1,899 patients with heart disease, focusing on a group with high levels of GDF11 and a similar protein called myostatin, which also happens to be a culprit in other diseases. Patients with high levels of the two proteins in their blood were less likely to die for any reason.

Using clinical imaging tests to gauge ventricular hypertrophy, the investigators also determined that lower levels of the protein were associated with thickening heart muscle.

"Individuals with heart disease who have relatively high concentrations of these proteins have much lower odds of dying and much lower odds of experiencing devastating outcomes that we associate with aging, including heart attacks, strokes and heart failure," said Peter Ganz, MD, professor of medicine and chief of cardiology at UCSF partner hospital San Francisco General Hospital and Trauma Center. "We also found that combined levels of GDF11 and myostatin in humans decline with advancing age, but that the rate of this decline varies among individuals."

Simply boosting levels of the two proteins, though, may not be the best approach to adding a new cardiovascular therapy to the pharmacopeia. A circulating protein called FSTL3 hampers the activity of both proteins, and blocking that target may be a safer and more efficient approach in the clinic.

The study, published online August 20, 2015 in the European Heart Journal, was funded by the U.S. Department of Veterans Affairs, the National Institutes of Health, the Robert Wood Johnson Foundation, the American Federation for Aging Research, and the Ischemia Research and Education Foundation. 

- here's the release