Researchers have discovered a previously unknown cardiac molecule that could provide a key to treating, and preventing, heart failure.
The newly discovered molecule provides the heart with a tool to block a protein that orchestrates genetic disruptions when the heart is subjected to stress, such as high blood pressure.
Researchers led by a team at Indiana University School of Medicine have discovered a cardiac compound that could lead to new treatment for heart failure.
Credit: Indiana University
When the research team, led by Ching-Pin Chang, M.D., Ph.D., associate professor of medicine at the Indiana University School of Medicine, restored levels of the newly discovered molecule in mice experiencing heart failure, the progression to heart failure was stopped. The research was published in the online edition of the journal Nature.
The newly discovered molecule is known as a long non-coding RNA. RNA's usual role is to carry instructions -- the code -- from the DNA in a cell's nucleus to the machinery in the cell that produces proteins necessary for cell activities. In recent years, scientists have discovered several types of RNA that are not involved in protein coding but act on their own. The role in the heart of long non-coding RNA has been unknown.
But the researchers determined that the newly discovered non-coding RNA, which they named Myheart -- for myosin heavy-chain-associated RNA transcript -- is responsible for controlling a protein called BRG1 (pronounced "berg-1"). In earlier research published in Nature in 2010, Dr. Chang and his colleagues discovered that BRG1 plays a crucial role in the development of the heart in the fetus.
But as the heart grows and needs to mature into its adult form, BRG1 is no longer needed, so very little of it is produced. That is, until the adult heart is subjected to significant stress such as high blood pressure or damage from a heart attack.
Dr. Chang's previous research showed that in those conditions, BRG1 re-emerges and begins altering the heart's genetic activity, leading to heart failure. At the same time, production of Myheart is suppressed, so BRG1 can latch onto the DNA and alter the genetic material unchecked.
In the current Nature paper, the researchers reported that in mice with stress-induced high levels of BRG1, they were able to restore Myheart to normal levels using gene transfer technology. Restoring Myheart levels blocked BRG1 actions and prevented heart failure, they said.
"I think of Myheart as a molecular crowbar that pries BRG1 off the genomic DNA and prevents it from manipulating genetic activity," said Dr. Chang, director of molecular and translational medicine at the Krannert Institute of Cardiology.
Although the results in mice would suggest testing Myheart against heart failure in humans, it is too large -- by molecular standards -- to be delivered as a drug, Dr. Chang said.
So he and his colleagues now are working to identify smaller portions of the Myheart molecule that are key to its ability to block BRG1. Such a subsection of the Myheart molecule could lead to a compound to test in human trials.
In addition to Dr. Chang and Pei Han, Ph.D., first author of the paper, investigators contributing to the research included Wei Li, Jin Yang and Peng-Sheng Chen of the IU School of Medicine; Chiou-Hong Lin, Ching Shang, Sylvia T. Nuernberg, Kevin Kai Jin, Weihong Xu, Chieh-Yu Lin, Chien-Jung Lin, Yiqin Xiong, Huan-Chieh Chien, Euan Ashley, Daniel Bernstein and Thomas Quertermous of the Stanford University School of Medicine; Bin Zhou of the Albert Einstein College of Medicine; and Huei-Sheng Vincent Chen of the Sanford/Burnham Medical Research Institute.
The research was supported by the American Heart Association (AHA; Established Investigator Award 12EIA8960018); the National Institutes of Health (NIH; HL118087, HL121197, HL109512, HL105194, HL78931, HL71140, HL116997, HL111770); California Institute of Regenerative Medicine (CIRM; RN2-00909, RB2-01512, RB4-06276); Stanford Heart Center Research Program; the IU School of Medicine-IU Health Strategic Research Initiative; the IU Physician-Scientist Initiative, endowed by Lilly Endowment; the Lucile Packard Foundation for Children's Health; the March of Dimes Foundation (#6-FY11-260); the Oak Foundation; and the Baxter Foundation.
Eric Schoch | Eurek Alert!
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences