Acute lung injury caused by cell death, high and potentially toxic concentrations of oxygen (hyperoxia) and the resulting excess fluid in the lungs (pulmonary edema) may be controlled by modulating levels of the angiopoietin2 (Ang2) protein, researchers at the School of Medicine report in the Nov. 5 online issue of Nature Medicine.
The study, which was completed in the laboratory of senior author Dr. Jack Elias, the Waldemar Von Zedtwitz Professor and chair of internal medicine, looked at the response to hyperoxic acute lung injury (HALI), first in mice and then in human adults and babies. The team found that mice in which the Ang2 gene was genetically eliminated or silenced lived longer and had evidence of decreased lung injury compared to mice in which the gene and protein were intact.
Levels of the Ang2 protein were then measured in the blood and lung fluid of adult patients and babies with acute lung damage and pulmonary edema. The team found that levels of Ang2, which is known to increase leaks in blood vessels and causes the death of endothelial cells that line the blood vessels, were higher in adult patients with acute lung injury and in babies born with respiratory distress syndrome who either went on to develop bronchopulmonary dysplasia or died.
"Mice without Ang2 seemed to be protected against hyperoxia," says first author Dr. Vineet Bhandari, assistant professor of pediatrics. "This protein seems to be a mediator of cell death in the settings of high oxygen concentrations in the lung causing acute lung injury and pulmonary edema."
Bhandari says the study is an example of true bench-to-bedside translational research. "All the work was initially done on mice in which we found that the Ang2 protein was involved in HALI," notes Bhandari. "We also defined how the protein creates lung injury and then we showed its clinical relevance by documenting its presence in human patients with acute lung injury."
In addition to acute lung injury and pulmonary edema, Bhandari says, an increase in Ang2 and cell death can be seen in other disorders such as heart attacks, stroke, eye disease in diabetics and brain tumors.
Other Yale authors on the study included Rayman Choo-Wing, Chun G. Lee, Zhou Zhu, Jonathan Nedrelow, Geoffrey Chupp, Xuchen Zhang, Michael Matthay, Lorraine Ware, Robert Homer and Patty Lee. The team collaborated with Anke Geick and Antonin R. de Fougerolles of Alnylam Pharmaceuticals, a biotechnology company focused on RNA interference therapeutics, which was used to silence the Ang2 gene.
--By Karen Peart
T H I S
W E E K ' SS T O R I E S
College leaders come to learn from Yale's sustainability goals
Trachtenberg to step down at year's end
Sherwin: Broader research approach needed today
Doctoral students are honored for their 'inspiring teaching'
ENDOWED PROFESSORSHIPS
Yochai Benkler named inaugural Field Professor
Oswald Schmitz has been named to Oastler chair
Henry Smith appointed to Johnston Professorship
School of Music announces two senior administrative appointments
Yale's World Performance Project will help launch . . .
Like father, like son: Yale tackle named NFF Scholar-Athlete
Students help in the fight against hunger via a silent auction
SCHOOL OF MEDICINE NEWS
Study finds link between HIV/AIDS and drug-resistant tuberculosis
Researchers implicate a protein in acute lung injury in children . . .
People often use food to cope with weight bias, study finds
Team describes structure of enzyme linked to Alzheimer's disease
In Memoriam: William A. Creasey
Book awards benefit area high school students and their school libraries
Campus Notes
Bulletin Home|Visiting on Campus|Calendar of Events|In the News
Bulletin Board|Classified Ads|Search Archives|Deadlines
Bulletin Staff|Public Affairs|News Releases|
E-Mail Us|Yale Home