Within heart cells, calcium plays a major role in orchestrating normal heart pump function. However, in diastolic failure the calcium signaling process is slowed; calcium levels rise to the peak needed for the squeezing action of the heart but don't then drop quickly enough for an efficient relaxation period – the condition known as diastolic heart failure.
University researchers were able to pinpoint a specific protein, parvalbumin – which aids in high-speed relaxation of fast twitching muscles in nature – and optimize it to become a calcium sponge for heart muscle. As a result, the optimized protein, ParvE101Q, soaks up excess calcium at a precise instant, allowing the heart to relax efficiently after contraction.
The advance offers a solid conceptual step forward in solving the puzzle of diastolic heart failure. The next step will be determining the best possible small molecule or gene delivery mechanism for the protein, which should allow the discovery to be used in clinics.
Their approach is outlined in the latest issue of Nature Medicine.
"In nature, there are unique organisms known to be able to contract and relax muscles quickly," said Joseph M. Metzger, Ph.D., a University of Minnesota Medical School professor and chair of the Department of Integrative Biology and Physiology. "We hoped research and discovery could help identify what was promoting this highly efficient activity so we could harness it for use in the heart. We've discovered that our optimized variation of parvalbumin can fulfill that role by treating diastolic heart failure."
According to Metzger, who also serves as the Maurice B. Visscher Endowed Chair in Physiology, the sponge mechanism works as a temporary depot for calcium along its normal pathway. It increases productivity in the relaxation phase of the heart cycle without negatively impacting the contracting phase.
If they can develop an ideal delivery system for the optimized protein, the researchers believe they may have found a unique clinical application to treat diastolic heart failure. Heart failure is a common killer of both men and women across the country and the rate of heart failure is increasing as our population ages and as the survival rate after recovery from first heart attack goes up.
"Heart disease and heart failure rates are growing, especially as our population ages. We hope this type of discovery may one day help pave the way to a better way to treat patients," said Metzger.
Collaborating with University of Minnesota investigators were researchers from the University of Miami (FL) Leonard M. Miller School of Medicine and The Ohio State University College of Medicine.
Funding for this project was provided in part by the National Institutes of Health via grants HL115876, HL59301, HL71016. Researchers also received support from the American Heart Association, the Lillehei Heart Institute, the University of Minnesota Medical School and the Visscher Endowed Chair.
Caroline Marin | EurekAlert!
Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn
New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology
Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.
Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
30.09.2016 | Event News
29.09.2016 | Event News
28.09.2016 | Event News
30.09.2016 | Materials Sciences
30.09.2016 | Earth Sciences
30.09.2016 | Life Sciences