Mar. 12, 2004 TORONTO – Researchers at St. Michael's Hospital examining a gene responsible for blood vessel development have discovered a possible link to a fatal respiratory disease in newborns which has no identified cause or cure. The study appears on-line today in Circulation Research, a journal published by the American Heart Association.
Results of the study, which examined mice lacking Endothelial NO Synthase (eNOS), a gene important in blood vessel growth, show that offspring of these animals had major defects in their lung development which resulted in respiratory distress and death.
"We found that the lungs of eNOS deficient mice share the same features as newborns with a fatal condition known as Alevolar Capillary Dysplasia (ACD)," says Dr. Duncan Stewart, Chief of Cardiology, and Associate Director, Basic Science Research, St. Michael's Hospital and the Dexter Man Chair of Cardiology, University of Toronto. "This discovery opens up a door into the possible cause of ACD. Knowing that there is a defect in vessel formation in the lung, we can examine potential therapies for ACD, including using techniques previously used for heart disease – such as stem cells and gene therapy – to stimulate the growth of blood vessels in the lung."
Infants born with ACD, a rare disease with no known cause or cure, develop respiratory distress and quickly become critically ill. The condition is always fatal. The small blood vessels and capillaries in the lungs are not properly formed and the lungs typically show a misalignment of the pulmonary veins.
At St. Michael's Hospital, Dr. Stewart and Robin Han, Research Associate, studied genetically engineered mice lacking the eNOS gene to determine the cause of neonatal death in the mutant animals' offspring. They discovered that this deficiency caused major defects in the lung, resulting in respiratory distress and death. Tests showed that small blood vessels and capillaries were not formed properly and there was a misalignment of pulmonary veins, features that are shared by newborns with ACD.
"We know from past research that eNOS is required for angiogenic genes to produce new blood vessels in the heart and elsewhere," says Dr. Stewart. Results of this study show that eNOS also plays a previously unrecognized role in lung development. "This is an exciting discovery as it is the first insight into the genetic basis of this human condition which is always fatal."
St. Michael's Hospital worked with researchers at The Hospital for Sick Children on the link between the deficient gene and ACD. "The aim of our research program is to understand the cellular and molecular physiological mechanisms that direct lung development with the long term objective to use the information to develop new therapeutic strategies or to improve existing therapies," says Dr. Martin Post, Head of the Lung Biology program and Interim Head of the Integrative biology program at The Hospital for Sick Children (Sick Kids) Research Institute, a Professor of Paediatrics in the Departments of Physiology, Laboratory Medicine and Pathology at the University of Toronto and a Canada Research Chair in Fetal, Neonatal & Maternal Health.
This work was supported by a grant form the Canadian Institutes of Health Research.
St. Michael's Hospital is a Catholic research and teaching hospital, fully affiliated with the University of Toronto, specializing in heart and vascular disease, diabetes comprehensive care, inner city health, trauma and neurosurgery, minimal access therapeutics, and mobility disorders.
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