The drug, a type of histone deacetylase (HDAC) inhibitor being evaluated in numerous ongoing clinical trials, has been shown to reverse the harmful effects of autophagy in heart muscle cells of mice. Autophagy is a natural process by which cells eat their own proteins to provide needed resources in times of stress. The new study appears in Proceedings of the National Academy of Sciences.
"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," said Dr. Joseph Hill, chief of cardiology and director of the Harry S. Moss Heart Center at UT Southwestern.
Dr. Hill, senior author of the study, and other researchers have shown previously that all forms of heart disease involve either too much or too little autophagy, normally an adaptive process. For example, in the presence of high blood pressure, the heart enlarges, or hypertrophies, and autophagy is turned on. Ultimately, the hypertension-stressed heart can go into failure.
Prior research from Dr. Hill's laboratory has shown that HDAC inhibitors blunt disease-associated heart growth, so researchers designed this study to determine what impact a particular type of HDAC inhibitor had on autophagy.
The researchers engineered mice with overactive autophagy and induced hypertrophy leading to heart failure. Scientists then gave the mice an HDAC inhibitor known to limit autophagy.
"The heart decreased back to near its normal size, and heart function that had previously been declining went back to normal," Dr. Hill said. "That is a powerful observation where disease regression, not just disease prevention, was seen."
Dr. Hill noted that the research that led to this finding started decades ago and included studies led by Dr. Kern Wildenthal, former president of UT Southwestern and now president of Southwestern Medical Foundation.
"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," Dr. Hill said. "That's the Holy Grail for a physician-scientist – to translate those sorts of fundamental molecular discoveries through preclinical studies and ultimately in humans."
Other UT Southwestern researchers involved in the study were Dr. Dian Cao, postdoctoral trainee in internal medicine; Dr. Zhao Wang, postdoctoral researcher in internal medicine; Dr. Pavan Battiprolu, postdoctoral researcher in internal medicine; Nan Jiang, research associate in internal medicine; Cyndi Morales, student research assistant in internal medicine; Yongli Kong, research scientist in internal medicine; and Drs. Beverly Rothermel and Thomas Gillette, both assistant professors of internal medicine.
The study was funded by the National Institutes of Health, American Heart Association, American Diabetes Association and the AHA-Jon Holden DeHaan Foundation.
Visit http://www.utsouthwestern.edu/heartlungvascular to learn more about UT Southwestern's heart, lung and vascular clinical services.
This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews
LaKisha Ladson | EurekAlert!
Speed data for the brain’s navigation system
06.12.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Health and Medicine
06.12.2016 | Life Sciences
05.12.2016 | Power and Electrical Engineering