A team of researchers at the University of Pennsylvania School of Medicine describe the interconnections between three-molecules that control fetal, heart-muscle-cell proliferation in a mouse model that will help cardiologists better understand the natural repair process after heart attacks and help scientists learn how to expand cardiac stem cells for regenerative therapies.
The research team, led by Jonathan Epstein, MD, chair of the Department of Cell and Developmental Biology, and Chinmay Trivedi, MD, PhD, an Instructor in the same department, report their findings in the cover article of the most recent issue of Developmental Cell.
The Penn team showed that an enzyme called Hdac2 directly modifies a protein called Gata4, and a third protein called Hopx, which appears to have adopted a new function. Hopx is a member of a family of ancient, evolutionally conserved proteins that normally bind DNA. In this case, however, rather than binding to DNA, it works to bring two other proteins, Hdac2 and Gata4, together. By performing this unexpected matchmaker function, Hopx helps to control the rate at which heart muscle cells divide.
“Although the degree to which hearts can repair themselves after injury is controversial, if there is a natural regeneration process, even if normally insufficient and modest, then approaches leveraging this insight this could be useful for boosting new growth so that it has a clinically significant effect,” says Epstein “We are eager to see if drugs like Hdac inhibitors will have this effect.”
The scientists found an unexpected function for Hdac2 as well. This enzyme normally acts as a switch that regulates how DNA is packaged inside the cell, and therefore how large groups of genes are turned on and off. Epstein said that his team was surprised discover that in the developing heart this packaging role was not the critical function.
“Rather, Hdac2 seems to be working directly on other proteins, and not on DNA structure, to control replication of heart muscle cells,” he says.
Hdac inhibitors are already in trials for cancer and one, valproic acid, has been used for decades to treat seizures. These inhibitors are a new class of agents that inhibit the proliferation of tumor cells in culture. Hdac inhibitors that are used to fight T cell lymphoma could possibly be used to enhance cardiac cell proliferation, say after a heart attack, when growing new heart muscle to replace damaged tissue would be is most needed.
“This could help to explain why Hdac inhibitors improve outcomes after heart attacks in animal models,” says Trivedi.
This research was funded by the National Heart, Lung and Blood Institute, the WW Smith Charitable Trust, and the American Heart Association.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.
Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.
Penn Medicine’s patient care facilities include:
The Hospital of the University of Pennsylvania – the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report.
Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.
Pennsylvania Hospital – the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and psychiatry & behavioral health.
Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.
Karen Kreeger | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences