Protein is potential new treatment target for adult pulmonary hypertension

October 17, 2011
Dr. Yunchao Su of Georgia's Health Sciences University has found the protein calpain holds promise for treating adult pulmonary hypertension. Credit: Phil Jones, GHSU photographer

A protein critical to development appears to have a grave impact on lungs exposed to smoking and air pollution, researchers report.

Blocking that protein, called calpain, in the lungs may prove an effective way to avoid narrow, scarred blood vessels and , said Dr. Yunchao Su, at Georgia Health Sciences University.

"Calpain enables the bad behavior that occurs in pulmonary hypertension," said Su, corresponding author of the study published in the .

Pulmonary hypertension is an often progressive and deadly condition in which tiny blood vessels that permeate the lungs narrow, raising blood pressure and eventually enlarging the pumping chamber of the heart as it struggles to get blood inside the lungs.

Babies with can have it, but in adults it can result from chronic , or COPD, primarily caused by smoking (emphysema is the most common form of COPD) or air pollutants, including second-hand smoke. Inflamed and poorly oxygenated lungs start producing growth factors and other measures to constrict blood vessels in an effort to restore balance between blood flow and . This works in the short term, Su said, but a chronic stimulus such as smoking can make, ongoing constriction debilitating or deadly. Treatment improves symptoms such as shortness of breath, but the only cure is a heart-lung transplant.

Researchers found calpain gets activated by growth factors released by stressed lung tissue then multiplies the vascular remodeling by cleaving TGFbeta, another growth factor typically inactive in the lungs. Cleaving TGFbeta releases a strong, active form that increases and collagen production. A similar process helps heal a cut on the hand, but inside the blood vessel it's counterproductive, Su said.

Additionally, in animal models of pulmonary hypertension as well as lungs removed from patients getting a transplant, the researchers found elevated levels of calpain. When they blocked its action by giving an inhibitor or removing its gene, TGFbeta was not activated and vascular remodeling and scarring as well as the heart damage were prevented. "The pulmonary process was close to normal," Su said.

Next steps include seeing whether the calpain inhibitor can stop cell proliferation and collagen synthesis in lung cells removed during a biopsy. Toxicology studies also will be needed before looking toward clinical trials, Su said.

He noted that a calpain inhibitor is likely not feasible for children because of the protein's importance in development. He envisions an inhalable version of the inhibitor to minimize any side effects in adults.

Su's earlier studies helped define calpain's role in cell proliferation when he found that lung cells in culture healed just fine after being cut until he added the calpain inhibitor. The work was published in 2006 in the The FASEB Journal. Su suspected then that calpain also had a role in pulmonary hypertension.

Explore further: Reversing smoke-induced damage and disease in the lung

Related Stories

Reversing smoke-induced damage and disease in the lung

October 13, 2011
By studying mice exposed to tobacco smoke for a period of months, researchers have new insight into how emphysema and chronic obstructive pulmonary disease (COPD) develops. In the October 14th issue of Cell they also report ...

When the lungs come under pressure

May 5, 2011
German scientists have found a way of treating pulmonary arterial hypertension.

Dr. Larissa Shimoda to discuss mechanisms of hypoxic pulmonary hypertension

April 11, 2011
When muscles and organs are deprived of an adequate supply of oxygen--a condition called hypoxia--the body's usual responses include increased circulation and a slight drop in blood pressure in the blood vessels serving the ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.