Inflammatory processes are prominent in various types of human and experimental
pulmonary hypertension (PH) and are increasingly recognized as major pathogenic components of pulmonary
vascular remodeling. Macrophages, T and B lymphocytes, and dendritic cells are present in the vascular lesions of PH, whether in
idiopathic pulmonary arterial hypertension (PAH) or PAH related to more classical forms of inflammatory syndromes such as
connective tissue diseases, human immunodeficiency virus (HIV), or other viral etiologies. Similarly, the presence of circulating
chemokines and
cytokines,
viral protein components (e.g., HIV-1 Nef), and increased expression of growth (such as
vascular endothelial growth factor and
platelet-derived growth factor) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors in these patients are thought to contribute directly to further recruitment of inflammatory cells and proliferation of smooth muscle and endothelial cells. Other processes, such as mitochondrial and
ion channel dysregulation, seem to convey a state of cellular resistance to apoptosis; this has recently emerged as a necessary event in the pathogenesis of pulmonary
vascular remodeling. Thus, the recognition of complex inflammatory disturbances in the
vascular remodeling process offers potential specific targets for
therapy and has recently led to clinical trials investigating, for example, the use of
tyrosine kinase inhibitors. This paper provides an overview of specific inflammatory pathways involving cells,
chemokines and
cytokines, cellular dysfunctions,
growth factors, and
viral proteins, highlighting their potential role in pulmonary
vascular remodeling and the possibility of future targeted
therapy.