Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

Chronic lung disease of prematurity, also referred to as bronchopulmonary dysplasia (BPD), is a common complication of preterm neonates with extremely low birth weight. Affected babies develop disease with high blood pressure in the lungs before the age of three months and many will die from this within one year of diagnosis. We have developed a model in newborn rats that resembles many characteristics of BPD in humans. Using this model, we recently identified that an imbalance between two different enzymes competing for the amino acid, L-arginine (nitric oxide synthase and arginase), contributes significantly to the development of experimental BPD. Indeed, treatment with an inhibitor of one of these enzymes, arginase, prevented many but not all features of the disease. Interestingly, we have since observed differences in the response to treatment with an arginase inhibitor that was dependent upon the sex of the animals. Preliminary data suggest a better treatment response in females compared with males. The overall goal of this proposal is to further characterize sex differences in response to injury and the effectiveness of preventive and rescue therapy. Together, our research will provide completely novel insights into sex differences and the response to therapy in chronic lung disease of prematurity.