Doctors speak of pulmonary hypertension (PH) when the pressure in the vessels from the heart to the lungs is permanently elevated.
This life-threatening condition can have various causes, but in the majority of those affected, pulmonary hypertension is caused by left heart failure (PH-LHD):
In this case, the heart muscle is too weak to pump the oxygen-rich blood from the left ventricle to the body, causing the blood to accumulate back into the pulmonary circulation.
This in turn puts a strain on the right side of the heart, which pumps the deoxygenated blood out of the body into the pulmonary artery. In consequence, pulmonary hypertension accelerates the progression of heart failure: a vicious cycle leading often to fatal consequences.
Synergy between research and clinic
Prof Christoph Knosalla and Dr Mariya Kucherenko, both from Charité's German Heart Centre (DHZC), and Prof Wolfgang Kübler, Director of the Institute of Physiology at Charité - Universitätsmedizin Berlin, have been intensively investigating the mechanisms that lead to PH-LHD for years. Their focus is on the remodelling processes in the vascular walls of the pulmonary arteries that lead to their stiffening. ‘Our collaborative project is a good example of the successful synergy between the DHZC and Charité as well as between basic research and clinical practice with the aim of achieving translational progress to improve clinical diagnostics and treatment,’ explains Prof Wolfgang Kübler.
RUNX2: key protein with a surprising effect
In a new research project, scientists are now focussing on the ‘RUNX2’ molecule. This protein is a transcription factor that can ‘switch on or off’ certain genes in cells.
During bone formation, RUNX2 ensures that cells store calcium and harden. However, if the protein becomes active in other tissues such as the pulmonary arteries, the cells of the arterial wall can transform into bone-like cells, which makes the vessels stiff and impedes blood flow. This connection has already been demonstrated in preclinical experiments with rats.
This is where the researchers begin: They want to further investigate the extent to which calcification in pulmonary arteries is also linked to RUNX2 in humans and identify the underlying molecular mechanisms.
Focus on new therapeutic approaches
In addition to calcification, RUNX2 can also influence other processes such as cell proliferation and cell ageing. The researchers would also like to investigate these ‘non-osteogenic’ effects of RUNX2 on the pulmonary arteries in more detail. Ultimately, the research trio's project is about the role of RUNX2 as a ‘therapeutic target structure’, i.e. new approaches to the treatment of pulmonary hypertension.
DFG funding paves the way
The necessary experiments are complex. The scientists have applied to the German Research Foundation - the largest research funding organisation in Germany - for funding. The DFG reviewers were impressed by the detailed documents submitted and approved the application. The project can now begin.
‘In view of the constantly growing number of people affected, the early and optimal treatment of heart failure is one of the greatest challenges for cardiovascular medicine. With our ever better understanding of pulmonary hypertension, we want to contribute to being able to offer better treatment options in the long term. We are therefore very pleased about the DFG's funding approval,’ says Prof Christoph Knosalla.
Source: Press release DHZC
