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.