Pulmonary hypertension: Molecular investigation of the remodelling processes in the heart

DZL scientist Prof. Dr. Soni Savai Pullamsetti and her team have discovered signalling pathways involved in developing right heart failure in patients with pulmonary hypertension. The findings, published in the journal Nature Cardiovascular Research, provide new biomarkers for diagnosis and targets for future therapies.

The function of the right ventricle plays a decisive role in the course of the disease in pulmonary hypertension patients. Progressive pulmonary hypertension can lead to pathological remodelling processes in the right ventricle that impair heart function. Early diagnosis of these changes is, therefore, essential to stop the progression of the disease and prolong the life of those affected.

The team led by Prof. Dr. Soni Savai Pullamsetti, Professor at the Cardiopulmonary Institute (CPI) Cluster of Excellence and the Institute for Lung Health (ILH) at Justus Liebig University Giessen, analysed tissue samples from 40 pulmonary hypertension patients and two animal models with right ventricular dysfunction. The aim was to determine which genes are active during the remodelling processes in the heart. Their research found differences in gene activity in individuals whose remodelling processes were either positive (compensated) or negative (decompensated) for heart function. Interestingly, they also found differences between the sexes, possibly due to lipid metabolism and oestrogen responses.

Biomarkers for assessing the course of the disease

Based on these findings on the altered gene activity, the researchers were able to detect five proteins in the patient's blood that could serve as biomarkers to assess the condition of the right ventricle. Combined with other diagnostic methods, these biomarkers could help predict the course of the disease better and earlier. In addition, the results lay the foundation for developing new therapeutic approaches against pulmonary hypertension and associated heart problems.

Original publication: Khassafi, F., Chelladurai, P., Valasarajan, C. et al. Transcriptional profiling unveils molecular subgroups of adaptive and maladaptive right ventricular remodelling in pulmonary hypertension. Nat Cardiovasc Res (2023). https://doi.org/10.1038/s44161-023-00338-3