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 | Source: EurekAlert!
Further information: www.umn.edu
More articles from Health and Medicine:
Targeted treatment can significantly reduce relapse in children with AML leukemia
09.12.2013 | Children's Mercy Hospital
Extensive variability in olfactory receptors influences human odor perception
09.12.2013 | Monell Chemical Senses Center
In power electronics systems bonded connections create the central electrical connections between adjoining surfaces.
The quality of these bonded connections is one of the main factors that determines the reliability and availability of drive systems in electric vehicles, and hence constitutes a major design challenge for German auto manufacturers aiming to electrify their vehicles.
Now the partners participating in the RoBE (Robust Bonds in ...
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
A genetic defect protects mice from infection with influenza viruses
A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses.
The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and ...
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
09.12.2013 | Materials Sciences
09.12.2013 | Life Sciences
09.12.2013 | Studies and Analyses
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News