An enzyme makes the mouse heart prone to chronic cardiac insufficiency – if it is suppressed, the heart remains strong despite increased stress.
Cardiologists at the Internal Medicine Clinic at Heidelberg University Hospital in cooperation with scientists at the University of Texas Southwestern Medical Center at Dallas and Göttingen University Hospital have now explained this key mechanism in a mouse model and thus discovered a promising approach for the systematic prevention of chronic cardiac insufficiency.
The study has now been published online before print in the prestigious journal “Proceedings of the National Academy of Sciences”.
Long-term high pressure and stenoses of the valves or aorta make the heart work harder. When it compensates by excessive muscle growth (cardiac hypertrophy), the pump function is affected – rhythm disorders or heart failure can be the result. Other risk factors are overweight and age – more than 40 percent of people over age 70 suffer from cardiac muscle hypertrophy.
Despite progress in medication, around 95,000 people in Germany die annually from the consequences of chronic cardiac insufficiency. “It is essential to find the molecules that are key to the development of cardiac insufficiency in order to develop new, more efficient treatment“ states Dr. Johannes Backs, head of a research group in the Department of Cardiology, Angiology, and Pneumonology (Director Prof. Dr. med. Hugo A. Katus) at Heidelberg University Hospital.
Enzyme activates stress response and hypertrophy of the heart
A key molecule for cardiac hypertrophy brought on by stress is the naturally occurring enzyme CaMKII delta (Calcium/Calmodulin-dependent kinase II delta). Dr. Backs’ international research team proved this in genetically modified mice that could no longer produce this enzyme by surgically obstructing the main aorta to put the heart under greater stress and thus simulate permanent high blood pressure or valve stenosis in humans. The anticipated enlargement of the heart was very slight – the animals were protected.
“With these mice, we succeeded for the first time in specifically suppressing the CaMKII delta enzyme and clarifying its function in detail,” said Dr. Backs. CaMKII delta has a direct effect on the cells’ stress response. If it is missing, certain information in cell DNA is not accessed that is normally activated by stress, leading to hypertrophy of the heart. “There was still some slight enlargement of the heart, but presumably not enough to cause cardiac insufficiency,” said Dr. Backs. Under normal conditions, the genetically modified mice are inconspicuous – their hearts function and react normally.
The function of CaMKII delta as an intermediate of the heart’s stress response is a possible approach for effective therapy – the Heidelberg researchers anticipate that agents that block only this function of the enzyme would prevent the heart muscle from reacting to overload. Other functions of CaMKII delta should not be affected in order to avoid harmful side effects.
Contact person:Dr. Johannes Backs
For questions from journalists:Dr. Annette Tuffs
Dr. Annette Tuffs | EurekAlert!
Researchers invent tiny, light-powered wires to modulate brain's electrical signals
21.02.2018 | University of Chicago
The “Holy Grail” of peptide chemistry: Making peptide active agents available orally
21.02.2018 | Technische Universität München
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Life Sciences
21.02.2018 | Life Sciences
21.02.2018 | Materials Sciences