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A Notch in Lung Arteries

 
  November, 2 2009 9:12
your information resource in human molecular genetics
 
     

The common signaling molecule Notch has a role in pulmonary arterial hypertension, often caused by insufficient oxygen reaching the lungs, as reported in a study published in Nature Medicine. This study highlights the importance of Notch in the development of pulmonary arterial hypertension, providing a novel target pathway for therapeutic intervention.

Notch signaling controls the proliferation of smooth muscle cells -- which line the lung arteries -- as well as the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive smooth muscle cell proliferation in small lung arteries, leading to elevation of blood pressure in the lung and consequently resulting in heart failure and death.

Patricia Thistlethwaite and her colleagues show that pulmonary hypertension in people is characterized by over-expression of the NOTCH3 gene in the smooth muscle cells of small lung arteries. The researchers also found that the severity of disease, both in humans and mice, correlates with the amount of NOTCH3 protein in the lung.

Mice lacking the Notch3 gene do not develop pulmonary hypertension in response to lack of oxygen. Moreover, pulmonary hypertension can be treated in normal mice by administering an inhibitor that blocks Notch3 activation in smooth muscle cells. Lastly, the scientists found that NOTCH3-mediated signaling drives smooth muscle cells towards a more undifferentiated, proliferative state.

Author Contact:

Patricia Thistlethwaite (University of California, San Diego, CA, USA)
E-mail: pthistlethwaite@ucsd.edu

Abstract available online.

(C) Nature Medicine press release.


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