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New therapeutic options are said to reduce heart muscle mass
Heart failure (heart failure) is one of the biggest problems for health systems worldwide and causes high costs. In Germany alone, the number of patients is estimated at up to three million. Researchers from Austria are working on new therapy concepts to improve cardiac function in heart failure.
Heart failure, which experts call heart failure, is one of the most common diseases in western countries. In Germany alone, the number of people affected is estimated at two to three million. If left untreated, the disease can be fatal. Scientists at the Medical University of Graz are working on new therapy concepts to improve heart function in heart failure.
Insufficient oxygen supply to the body via the blood
Heart failure is spoken of when an adequate supply of oxygen to the body via the blood is no longer guaranteed, explains the Medical University of Graz in a message.
In around half of the patients, heart failure can be attributed to a reduced pumping capacity of the heart. And the other half of those affected suffer from increased stiffness of the ventricles.
"This stiffening of the ventricles is known in medicine as" Heart Failure with preserved Ejection Fraction - HFpEF for short - and is associated with poor prognosis and quality of life, "explains Markus Wallner from the clinical department for cardiology at the Medical University of Graz.
Despite intensive research efforts, there is currently no prognosis-improving therapy for patients with HFpEF. The researcher, together with international colleagues, has taken this supply gap as the focus for his scientific work.
HDAC inhibitors as a therapy option
As part of a research stay at Temple University in Philadelphia (USA), the Austrian scientist worked with colleagues to develop a preclinical model that shows many important cardiopulmonary changes, such as HFpEF, and according to the ESC Heart Failure Guidelines - ESC stands for European Society of Cardiology - all criteria are met in order to be able to make an HFpEF diagnosis.
"In the next step, we examined the cardiopulmonary and metabolic effects of SAHA, a histone deacetylase (HDAC) inhibitor in this model," explains Wallner. HDAC inhibitors are currently approved for the treatment of various tumors, but not for the treatment of heart failure.
HDAC inhibitors cause chemical attachment of acetyl groups in the body, which means that they play an important role in gene expression. These active substances modify and regulate cell functions.
The research results were published in the scientific journal "Science Translational Medicine" and resulted from an international research cooperation between the Medical University of Graz with CBmed, Temple University, Philadelphia and the University of Colorado.
Holistic improvement of cardiac function
The research team found that if the left ventricular hypertrophy was already pronounced - a pathological enlargement of the heart muscle of the left ventricle - the HDAC inhibition in the HFpEF model led to a significant decrease in the heart muscle mass.
The treatment also led to an improved contractility of the heart and a decrease in the left ventricular filling pressure, which is pathologically increased in the case of cardiac insufficiency.
"The filling pressure describes the pressure that prevails in the ventricle at the end of the relaxation phase of the heart," explains Wallner. The improved relaxation of the heart in the laboratory model could be attributed, among other things, to an improvement in myofibrillary relaxation, that is to say an improvement in the relaxation capacity in the heart muscle fibers.
"As a result of the holistic improvement in cardiac function, it was also possible to reduce the pulmonary pressure conditions and thereby improve lung function," added Wallner to another important research result.
Finally, the scientists were able to demonstrate positive effects in the skeletal muscles and the mitochondrion.
No effective therapy options available yet
According to the information, some of these promising effects of HDAC inhibitors could also have a positive effect on patients with HFpEF.
"New therapy concepts for HFpEF are urgently required because the prognosis and quality of life of patients with HFpEF are poor and so far no effective therapy options are available," summarizes Wallner.
The research results now available make an important contribution in order to be able to investigate the effects of HDAC inhibitors in heart failure in the context of clinical studies in the future. (ad)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
- Medical University of Graz: In rhythm: heart failure, (accessed: January 12, 2020), Medical University of Graz
- Markus Wallner, Deborah M. Eaton, Remus M. Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Jichuan, Mark Y. Jeong, Ying H. Lin, Giulia Borghetti, Sandy T. Baker, Huaqing Zhao, Jessica Pfleger, Sandra Blass , Peter P. Rainer, Dirk von Lewinski, Heiko Bugger, Sadia Mohsin, Wolfgang F. Graier, Andreas Zirlik, Timothy A. McKinsey, Ruth Birner-Gruenberger, Marla R. Wolfson, Steven R. Houser: HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction, in: Science Translational Medicine, (published: 08.01.2020), Science Translational Medicine