Boosting FoxO1 to Treat Pulmonary Hypertension

Researchers here uncover an interesting role for one of the forkhead box (FOX) proteins, and the potential basis for a treatment for pulmonary hypertension:

An estimated 100 million people worldwide suffer from pulmonary hypertension. The disease is characterised by progressive narrowing of the pulmonary arteries. The reduced diameter of the vessels leads to poor perfusion. The right ventricle tries to compensate by increasing its pumping action. This, in turn, increases the blood pressure in the pulmonary arteries. In the course of time, chronic overload damages the heart. The result is cardiac insufficiency, also known as congestive heart failure. Several forms of treatment developed in recent years aim mainly to alleviate the symptoms and relieve strain on the heart. Pulmonary hypertension, however, is still incurable, not least of all due to insufficient knowledge of what causes the disease at the molecular level.

[Scientists] have now achieved a major advance. In transcription factor FoxO1 they have identified a key molecule that plays a decisive role in the regulation of cell division in vascular wall cells and the lifespan of the cells. "The vessel walls of pulmonary arteries are constantly being renewed. A complex interplay of many factors normally ensures that the ratio between dividing and dying cells is balanced." The researchers found an important clue about the central role of FoxO1 in tissue samples from pulmonary hypertension patients: "In these patients, FoxO1 is not sufficiently active, so that the activity of various genes is not properly controlled. If we switch off FoxO1 by means of genetic or pharmacological intervention, the vascular wall cells divide more frequently." Consequently, pulmonary hypertension develops.

Reduced FoxO1 activity is therefore an important factor in the development of pulmonary hypertension. In further experiments it was found that certain growth factors and chemical messengers are responsible for reduced FoxO1 activity. Accordingly, pathological cell division in pulmonary vessel walls normalized when the researchers boosted FoxO1 activity. "Rats suffering from pulmonary hypertension were essentially cured." Based on these positive findings, the scientists are optimistic that the study findings can be used to develop a novel therapeutic approach.

Link: http://www.mpg.de/8721341/PullamsettiFoxO1

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