Blocking that protein, called calpain, in the lungs may prove an effective way to avoid narrow, scarred blood vessels and pulmonary hypertension, said Dr. Yunchao Su, pharmacologist 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 Journal of Clinical Investigation.
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 heart defects can have it, but in adults it can result from chronic obstructive lung disease, 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 oxygen levels. 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 cell proliferation 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.
Dr. Wanli Ma, former postdoctoral fellow in Dr. Su's lab, is first author. GHSU coauthors include Dr. Weihong Han, research associate, and Dr. Haroldo Toque, a postdoctoral research associate in Dr. William Caldwell's lab.
Toni Baker | EurekAlert!
Speed data for the brain’s navigation system
06.12.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Earth Sciences
07.12.2016 | Earth Sciences
07.12.2016 | Materials Sciences