Figure 11. The role of inflammation in the pathogenesis of PAH.

Initial inflammatory stimuli can occur in the form of infectious or foreign antigens or autoimmune disease, leading to an appropriate, but potentially excessive, immune response. The host immune response to these varied stimuli results in the release of pro-inflammatory cytokines, which can recruit bone marrow-derived cells, stimulation of resident inflammatory cells, and endothelial cell dysfunction. Endothelial cell injury and the cellular response can increase endovascular thrombosis. A network of cytokines released by the inflammatory and endothelial cells can also cause aberrant PASMC proliferation. The triad of endothelial cell proliferation, PASMC proliferation, and thrombus formation contributes to PAH. Pro-inflammatory cytokines and cell-cell interactions can potentially be therapeutically targeted.

Abbreviations: EGF: epidermal growth factor; HIMF: hypoxia induced mitogenic factor, also called RELMa and FIZZ1; NO: nitric oxide; PDGF: platelet derived growth factor; RANTES; TNFα: tumor necrosis factor-alpha.

Figure and legend contributed by Drs. Brian Graham and Rubin Tuder, University of Colorado at Denver.