Treating Pulmonary Hypertension

Protein discovery may lead to new treatments for adult pulmonary hypertension

(RxWiki News) A critical protein has been found to have a serious impact on lungs exposed to air pollution or smoking. Blocking that protein may be an effective way to prevent narrowed blood vessels and pulmonary hypertension.

Pulmonary hypertension occurs when tiny blood vessels in the lungs narrow, causing elevated blood pressure in the lungs, and ultimately enlarging the heart's pumping chamber as it struggles to get blood inside the lungs. It is progressive and can be a fatal condition.

"Quit smoking and avoid polluted air."

Pulmonary hypertension in adults is most often caused by chronic obstructive pulmonary disease, developed by smoking cigarettes, or exposure to air pollutants.

Dr. Yunchao Su, author of the research and a pharmacologist at Georgia Health Sciences University, said that the protein called calpain enables the bad behavior that occurs in pulmonary hypertension.

When the lungs are inflammed and not receiving enough oxygen, they begin producing growth factors to constrict blood vessels to strike a balance between oxygen levels and blood flow, though this can only work short term.

Investigators discovered that calpain is activated by the growth factors released to the stressed lung tissue.  It then multiplies the vascular remodeling by "cleaving" the usually inactive growth factor TGFbeta. The cleaving releases a stronger, more active form that rapidly increases the creation of new cells and collagen.

During the study, researchers found elevated levels of calpain both in animal models and also in lungs removed from patients during transplant. They found that an inhibitor to block the protein, or removal of its gene, meant that TGFbeta was not activated, preventing vascular changes, scarring and heart damage. With the protein blocked, Dr. Su said the pulmonary process became almost normal.

Dr. Su anticipates creating an inhalable version of the inhibitor to cut down on the possibility of side effects in adults. It is unlikely that the treatment wlll be feasable for children because the protein also is important in development.

Researchers next plan to determine whether the calpain inhibitor can stop cell and collagen proliferation in lung cells removed during a biopsy.

The research was published in the Journal of Clinical Investigation.

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Review Date: 
October 20, 2011