Cellular and Molecular Mechanisms in Pulmonary Hypertension
Projektledare Karin Tran Lundmark
Pulmonary hypertension (PH) is a life‐threatening condition, which untreated leads to right heart failure and death. The disease is characterized by three major pathological changes in the pulmonary arterial wall: 1) vasoconstriction, 2) cell proliferation and remodeling, and 3) in situ thrombosis. Current treatment with prostaglandin analogues, nitric oxide, endothelin receptor antagonists, and phosphodiesterase‐5 inhibitors, target mainly the vasoconstrictive component and provide limited improvement of symptoms and prognosis. Perlecan and versican, two proteoglycans in extracellular matrix, are important regulators of smooth muscle cell proliferation in peripheral vascular disease, but their role in the pulmonary vasculature is unknown. Our hypothesis is that perlecan is inhibitory while versican is stimulatory for the proliferation of pulmonary artery smooth muscle cells (paSMC). Our aim is therefore to investigate the role of perlecan and versican in the regulation of the proliferative component of PH; and to evaluate the efficacy of experimental drugs that alter the levels of perlecan and versican in pulmonary arteries.