Pulmonary hypertension is a rare but life-threatening condition in which blood pressure rises dangerously in the arteries of the lungs.
If left untreated, it can be fatal within just two years. While current treatments can slow the disease, there is still no cure.
Now, researchers in Germany have identified a previously unknown factor that may play an important role in how the disease develops.
The discovery was made by research teams from Ruhr University Bochum and University of Bonn. Their findings were published in the Proceedings of the National Academy of Sciences.
Pulmonary hypertension happens mainly because the blood vessels in the lungs become narrowed.
When these vessels tighten, there is less space for blood to flow through, causing pressure to build up. Over time, this extra strain can damage the heart and lungs.
Under normal conditions, the body carefully regulates blood vessel width. Cells lining the blood vessels release a molecule called nitric oxide, or NO.
This molecule signals the surrounding muscle cells to relax, allowing the vessels to widen and blood to flow more easily.
The relaxation process depends on an enzyme called soluble guanylate cyclase, or sGC, which helps produce another molecule that lowers calcium levels in muscle cells, leading to relaxation.
At first glance, the protein beta arrestin 1 does not seem related to this process. It was previously known mainly for regulating other signaling pathways in cells. However, the German research team suspected it might have a broader role.
To investigate, they studied genetically modified mice that lacked either beta arrestin 1 or beta arrestin 2. The results were striking. Mice missing beta arrestin 2 showed no major differences compared to normal mice. But mice lacking beta arrestin 1 developed pulmonary hypertension. When given nitric oxide, their lung blood vessels did not widen properly.
Further experiments revealed why. Beta arrestin 1 physically binds to soluble guanylate cyclase and helps maintain its function. The enzyme sGC depends on a tiny iron-containing structure called a heme group. For sGC to respond properly to nitric oxide, the iron in this heme must be in the correct chemical state. Beta arrestin 1 helps transport another enzyme that restores the iron if it becomes oxidized, effectively “recharging” sGC so it can respond to nitric oxide again.
Without beta arrestin 1, this repair process does not work efficiently. As a result, blood vessels cannot relax as they should, contributing to increased lung blood pressure.
The researchers say this discovery raises important new questions. For example, could some patients with pulmonary hypertension have genetic changes that affect beta arrestin 1? In the future, scientists hope it may be possible to develop drugs that boost or activate beta arrestin 1, potentially leading to more effective treatments.
Although much work remains, identifying this new piece of the puzzle brings researchers one step closer to better understanding and treating this serious disease.
