Elastase and the Pathobiology of Unexplained Pulmonary Hypertension

¹ From the Division of Cardiovascular Research, Research Institute, The Hospital for Sick Children, and from the Departments of Pediatrics, Pathology and Medicine, University of Toronto, Toronto, Ontario, Canada

Marlene Rabinovitch, MD, Director, Division of Cardiovascular Research, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; email: mr{at}sickkids.on.ca

Our laboratory has focused on the increased activity of an endogenous vascular elastase in the pathobiology of pulmonary hypertension and on the mechanisms by which it is upregulated and by which it orchestrates abnormal remodeling of the vessel wall, specifically the induction of growth factors, the induction of the glycoprotein tenascin, which amplifies the proliferative response, and fibronectin, which is critical to the process of smooth muscle migration in the context of neointimal formation. We explore strategies by which targetting these processes might arrest progression or induce regression of pulmonary vascular disease associated with unexplained pulmonary hypertension.