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Oct 26, 2009

Researchers Identify Protein that Plays a Role in Pulmonary Arterial Hypertension

  • A protein that promotes the development of pulmonary arterial hypertension in humans and mice has been discovered by researchers at the University of California, San Diego (UCSD). Patricia Thistlethwaite, M.D., Ph.D., and colleagues from UCSD describe the genetic pathway by which vascular smooth muscle cells associated with pulmonary arterial hypertension are switched on to proliferate by a receptor protein called Notch-3.

    The researchers were also able to block and reverse this pathway in mice. The paper describing the research was published online in Nature Medicine on October 25 and is called “Notch3 signaling promotes the development of pulmonary arterial hypertension.”

    “The UCSD team found that pulmonary hypertension is characterized by overexpression of Notch-3 and that the severity of the disease correlates with the amount of this protein in the lung,” explains Dr. Thistlethwaite. “We showed that a mouse model lacking this protein does not develop pulmonary hypertension and in addition, that the disease can be effectively treated with an enzyme called γ-secretase inhibitor, which blocks Notch-3 activation.”

    Mice with pulmonary arterial hypertension that were treated with the γ-secretase inhibitor showed reversal of the disease. Forms of this drug are currently in use in Phase I trials for the treatment of Alzheimer's disease. 

    “Current drugs to treat pulmonary arterial hypertension focus on dilating the arterial vessels but do not address the eventual thickening of the artery walls,” points out co-author Stuart Jamieson. “Fortunately, by identifying this drug target, it seems we are now on the right path to developing an intervention that prevents abnormal cell proliferation.”

     



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