News - Hypertension Week of Feb. 9, 2003/ Vol. 2 No. 06

Study: Over-Active Gene Can Cause Pulmonary Hypertension

The molecular events triggered by an over-active gene can lead to pulmonary hypertension, according to University of California at San Diego (UCSD) researchers.

The findings, reported in the Feb. 6 issue of the New England Journal of Medicine, offer the first specific molecular targets for development of new therapies. Currently, the only treatment for most types of pulmonary hypertension is a lung transplant.

Pulmonary hypertension is acquired from diverse causes such as congenital heart defects, autoimmune disease, left-sided heart failure, blood clots in the lungs, drug interactions or vascular diseases. A handful of patients inherit a rare form of the disease from a genetic mutation.

Behind the development of pulmonary hypertension, according to the researchers, is a gene called angiopoietin-1, which is normally involved in smooth-muscle growth in newly developing embryonic blood vessels. The gene can be inappropriately turned on in adulthood.

When that happens, this over-expressed gene then initiates a molecular chain of events that causes muscle cell proliferation within the lining of the lung's blood vessels. As the vessel wall thickness grows, the small lung arteries become progressively narrowed and blocked.

"We wondered whether a common molecular mechanism underlies all the different causes of pulmonary hypertension as well as the inherited form," said study's study author Dr. Patricia Thistlethwaite, an assistant professor in the UCSD Division of Cardiothoracic Surgery.

The investigators reasoned that since angiopoietin-1 was involved in
embryonic smooth-muscle development, an aberrant turn-on of this gene might cause the over-growth of muscle tissue in adults that is characteristic of pulmonary hypertenison.

The researchers affirmed their hypothesis after examining lung biopsies from pulmonary hypertension patients who had acquired the condition from a variety of causes and a control group who were undergoing lung surgery without pulmonary hypertension.

Currently, the researchers are working on potential inhibitors of
angiopoitin-1, to see if they can stop pulmonary hypertension in rodent models.

Other sources: University of California at San Diego, NEJM 2003:348 500-509