Characterizing and treating pulmonary pathology in Marfan syndrome (847.2)

Abstract

Marfan syndrome (MFS) is a connective tissue disorder that leads to life‐threatening complications. While current research focuses on the cardiovascular pathogenesis of MFS, MFS also gives rise to serious pulmonary disease, the study of which is severely lacking. Therefore, we aimed to characterize lung function in a murine model of MFS and investigate the pharmacological effectiveness of Losartan, an angiotensin II receptor type I blocker, and Sildenafil (Viagra), a phosphodiesterase type 5 inhibitor. Our studies demonstrate that MFS mice have significant dilation of the pulmonary artery with highly significant changes lung function measurements as well as significant airspace widening and lung destruction. Notably, Losartan was able to prevent airspace widening and Sildenafil was effective at preventing pulmonary artery dilation but did not improve lung function. This study is the first to report changes in the pulmonary artery and in vivo lung function measures in MFS and investigate the use of Losartan and Sildenafil. As such, it elucidates key aspects of MFS pathogenesis and pharmacological treatment and guides future investigations of pharmacological interventions for MFS pulmonary dysfunction. Grant Funding Source: Supported by The Canadian Institutes of Health Research