Key Protein Linked To Pulmonary Arterial Hypertension Identified

University of California, San Diego, researchers have made groundbreaking discovery by identifying a key protein that promotes the development of pulmonary arterial hypertension in humans and mice.

The finding has implications for future drug therapies that may extend the life of patients with pulmonary arterial hypertension and prevent the need for lung transplantation, currently the only cure for this debilitating disease.

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In the study, Dr. Patricia Thistlethwaite and colleagues have described the genetic pathway by which vascular smooth muscle cells linked with pulmonary arterial hypertension are switched on to proliferate by a receptor protein called Notch-3.

The finding helped researchers to block and reverse the pathway of disease in mice.

"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. 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 -secretase inhibitor, which blocks Notch-3 activation," Nature quoted Thistelthwaite as saying.

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In the laboratory, mice with pulmonary arterial hypertension that were treated with the -secretase inhibitor showed reversal of the disease.

Forms of this drug are currently in use in Phase 1 trials for the treatment of Alzheimer's disease.

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Pulmonary arterial hypertension is more common in the human population than is currently realized, and unfortunately, is often fatal," said co-author Dr. Stuart Jamieson.

"Current drugs to treat pulmonary arterial hypertension focus on dilating the arterial vessels but do not address the eventual thickening of the artery walls. Fortunately, by identifying this drug target it seems we are now on the right path to developing an intervention that prevents abnormal cell proliferation," he added.

The study has been published online in Nature Medicine.

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