Inflammatory mechanisms in the pathogenesis of pulmonary arterial hypertension

Inflammation is a prominent feature of human and experimental pulmonary hypertension (PH) as suggested by infiltration of various inflammatory cells and increased expression of certain cytokines in remodeled pulmonary vessels. Macrophages, T and B lymphocytes, and dendritic cells are found in the vascular lesions of idiopathic pulmonary arterial hypertension (PAH) as well as in PAH associated with connective tissue diseases or infectious etiologies such as HIV. In addition, PAH is often characterized by the presence of circulating chemokines and cytokines, increased expression of growth (such as VEGF and PDGF) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), which directly contribute to further recruitment of inflammatory cells and the pulmonary vascular remodeling process. These inflammatory pathways may thus serve as potential specific therapeutic targets. This article provides an overview of inflammatory pathways involving chemokines and cytokines as well as growth factors, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy.