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2025-02-05

New Theory on the Development of Pulmonary Arterial Hypertension: The Role of Lysosomes

News 2025-063 EN

Pulmonary arterial hypertension (PAH) is a rare disease, but one that can be fatal for those affected, as blood pressure is elevated in the arteries that lead from the heart to the lungs. This is caused by the narrowing of these vessels, which impedes blood flow and places a significant strain on the heart. The exact causes remain unclear. Researchers from Justus Liebig University Giessen at the DZL site UGMLC have proposed a new theory that focuses on the interaction of individual cellular components, known as organelles: the disease could arise if the interaction between lysosomes and other organelles is disrupted. The study has been published in the renowned journal Science.

Lysosomes are components of a cell responsible for "recycling" or disposing of waste products. They play a crucial role in cellular metabolism and the immune system. Lysosomes constantly interact with other cellular components. However, if this process is disrupted, severe diseases such as metabolic disorders or cancer can occur.

A research duo from JLU has proposed the hypothesis that PAH may also be caused by a failure in the proper interaction between lysosomes and other organelles: "This disruption impairs the function of the lysosomes, which in turn can have serious effects on other cellular components such as mitochondria, responsible for cellular energy production, and also on lipid metabolism in the cell nucleus," explains Prof. Soni Savai Pullamsetti, Professor of Epigenetics of Pulmonary Vessels at JLU and scientific coordinator for the DZL disease area Pulmonary Hypertension. This, in turn, can lead to genetic anomalies in the vascular cells, which are characteristic of pulmonary arterial hypertension.

In their study, the researchers also outline a potential approach to correct this disruption: "One possibility could be to activate NCOA7 in the cell. This protein is involved in switching certain genes on and off that are important for cellular metabolism," says Prof. Rajkumar Savai, also DZL PI and Professor at the Institute for Lung Health at JLU, as well as head of Oncological Basic Research at the University Hospital Gießen and Marburg. It is also conceivable to epigenetically modify the interaction between lysosomes and other organelles in order to potentially cure PAH in the future.

 

Original article: https://www.uni-giessen.de/de/ueber-uns/pressestelle/pm/pm20-25pah

Original publication: Pullamsetti SS, Savai R. Decoding lysosome communication. Science. 2025 Jan 24;387(6732):359-361. doi: 10.1126/science.adv1201. Epub 2025 Jan 23. PMID: 39847645.

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