Their latest research reveals that impaired energy production in heart muscle may underlie heart failure in some hypertensive patients. The researchers assert that a molecular factor involved in maintaining the heart's energy supply could become a key to new approaches to prevent or treat heart failure.
The molecular factor, a protein called estrogen-related receptor alpha (ERR alpha), helps the heart keep up with energy-draining conditions like high blood pressure, which makes the heart work harder to pump blood. In the July issue of Cell Metabolism, Kelly and his colleagues report that mice born without any ERR alpha developed symptoms of heart failure when their hearts were forced to pump against high pressure. The hearts of normal mice took that pressure overload in stride and stayed healthy. Those contrasting outcomes suggest that heart health greatly depends on ERR alpha.
"The stress of a cardiac pressure overload asks heart muscle to manufacture more high energy compounds, and without ERR alpha, they can't do it," explains Kelly, the Tobias and Hortense Lewin Professor and Chief of the Cardiovascular Division. "You could say that in high blood pressure conditions, the heart fails because it becomes energy starved. And if you could feed the heart — by using a drug that enhances ERR, for example — you might enable the heart to better keep pace with its energy requirements."
Although preventions and treatments are now available for heart failure due to high blood pressure, almost all of those drugs act outside the heart by dilating blood vessels throughout the body to reduce resistance. In the future, doctors might look for diminished energy capacity in the hearts of hypertensive patients and administer drugs that would rev up energy-producing pathways such as those controlled by ERR alpha, according to Kelly. Kelly is also director of the Center for Cardiovascular Research and professor of medicine, of pediatrics and of molecular biology and pharmacology.
ERR alpha sits in the nucleus of cells and senses how much energy is needed. When a heart cell finds itself short on energy, say because it's being called on to contract harder or faster, its ERR is activated by an inducible co-activator called PGC-1, turning on genes that increase the heart's capacity to burn fats for fuel.
In mice that lacked ERR alpha and that were exposed to pressure overload, the researchers observed signs of early heart failure: the mouse hearts dilated and didn't contract effectively, the heart walls thinned, fibrous connective tissue accumulated and some heart cells died. They also saw that the hearts had depleted fuel reserves.
Kelly indicates that these studies show for the first time that changes in the ability of the heart to produce energy lead to heart failure in some cases. "ERR and some of its partners in the cell are a little like puppeteers controlling the expression of genes for energy production," Kelly says. "This research is especially exciting because ERR can be activated with small compounds, making it a good target for drugs."
Gwen Ericson | EurekAlert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
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