Unveiling the Complexity of Right Heart Failure Through Interdisciplinary Research

The progressive inability of the heart to pump sufficient blood through the body is an incurable condition with a poor prognosis. This condition, which can affect both the right and left ventricles, is known as chronic heart failure or heart insufficiency. It is often the end stage of various heart diseases and is among the leading causes of death worldwide, with a rising trend. Particularly, the specific processes involved in right heart failure are relatively less researched compared to the more common left heart failure. An interdisciplinary team at the Justus Liebig University Giessen (JLU), including DZL scientists and led by physiologist Prof. Dr. Susanne Rohrbach and pharmacologist Prof. Dr. Michael Kracht, has now published a study in "Nature Cardiovascular Research" addressing this gap.

"In right heart failure, the right ventricle can no longer pump enough blood through the lungs, leading to a backlog into the liver and other organs, and resulting in insufficient oxygenation of the blood," explains Prof. Rohrbach. "There are several causes for this, such as high blood pressure in the pulmonary circulation, narrowing of the pulmonary arteries, or heart valve defects."

Though often equated, there are significant differences between the left and right ventricles. The right ventricle, where the blood pressure is lower, has a thinner muscle layer, less force, and a more compliant heart wall. "These differences and the lack of response of right heart failure to conventional medications for left heart failure led to the question of what molecular changes occur in the course of chronic right heart disease," explains Prof. Michael Kracht from the Rudolf Buchheim Institute for Pharmacology at JLU. "Of particular interest to us was the right ventricle's ability to compensate for a pumping weakness through remodeling processes over an extended period before it eventually fails, leading to terminal right heart failure."

The researchers used complex bioinformatic methods to reconstruct functionally related genetic networks, whose activation correlates with the severity of right heart failure. They compared the gene activities of heart muscle cells from a specially established rat model with tissue samples from patients suffering from a chronic form of pulmonary hypertension with right heart strain. The research findings can help understand the causes of the disease and develop new therapies.

"We found groups of genes that indicate the transition from a compensated right heart function to a worsening right heart failure. Some of these genes are important for the connective tissue remodeling of heart tissue and could serve as biomarkers or targets for new drugs in the future," emphasizes Prof. Kracht. "Other genes have been scarcely studied, such as proenkephalin, whose gene products can impair the function of heart muscle cells. Our results show that right heart failure is not caused by a single gene, but by groups of interacting genes. In the future, it will be important to target these gene networks specifically," adds Prof. Rohrbach.

The interdisciplinary investigation of pulmonary hypertension and right heart failure represents the core competence of the Giessen Collaborative Research Center (CRC) "Pulmonary Hypertension and Cor Pulmonale." "The study exemplifies how diverse resources are combined to develop new insights and therapeutic approaches. Numerous researchers from various sub-projects of the CRC contributed with sample material, data sets, and specific tests to complement this study," explains Prof. Dr. Norbert Weißmann, DZL scientist and spokesperson of the CRC.