Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension

Chronic pulmonary hypertension leads to structural alterations of the lung vessels. The pathophysiology of this remodelling process is still poorly understood. Furthermore, the structural damage of the lung vessels limits the clinical success of vasodilator treatment. Given a genetic susceptibility, shear stress and inflammation are the principal pathogenetic factors involved in lung vessel remodelling. In this overview, we compared the lung vascular histology of patients with unexplained pulmonary hypertension, scleroderma, or acquired immune deficiency syndrome (AIDS)-associated pulmonary hypertension. We demonstrate the presence of inflammatory cells (T- and B-lymphocytes and macrophages) in plexiform lesions and discuss the potential role of growth factors (platelet-derived growth factor (PDGF), transforming growth factor-beta TGF-beta) and vascular endothelial growth factor (VEGF) in pulmonary hypertensive remodelling. Ultimately, we need to develop an in-depth understanding of the key mechanisms of gene expression and signalling pathways, which transduce signals generated from increased chronic shear stress (or from chronic hypoxia) and lead to vascular injury and repair.