Smouldering fire or conflagration? An illustrated update on the concept of inflammation in pulmonary arterial hypertension

Inflammatory mechanisms involved in pulmonary arterial hypertension (PAH) pathogenesis.

The two types of mechanism that underlie pulmonary arterial hypertension pathogenesis.

Structural alterations as a cause of inflammation. Disturbed blood flow and stiffness-induced inflammation. ECM: extra-cellular matrix.

Hypoxia-induced inflammation. BDNF: brain-derived neurotrophic factor; PAEC: pulmonary arterial endothelial cell; PASMC: pulmonary arterial smooth muscle cell; TSLP: thymic stromal lymphopoietin; VEGF: vascular endothelial growth factor.

Pattern recognition receptor (PRR)-induced inflammation in pulmonary arterial hypertension. DAMP: damage-associated molecular pattern; HMGB1: high mobility group box-1; LPS: lipopolysaccharide; PAMP: pathogen-associated molecular pattern; RAGE: receptor for advanced glycation end products; TLR4: toll-like receptor 4.

Transcription factors linking vascular remodelling and inflammation. ERG: ETS-related gene; FLI-1: Friend leukaemia integration 1 transcription factor.

Inflammation as a cause of structural alterations: autoimmunity in pulmonary arterial hypertension (PAH). CCL20: chemokine (C-C motif) ligand 20; CXCL13: chemokine ligand 13; FOXP: Forkhead box P; IL-17: interleukin-17; MHC: major histocompatibility complex; MoDC: monocyte-derived dendritic cell; NK: natural killer cell; NKT: natural killer T-cell; Th17: T-helper 17; tLT: tertiary lymphoid tissue.

Heritable pulmonary arterial hypertension: predisposing mutations involved in immune regulation. BMPR2: bone morphogenetic protein receptor type 2; ER: endoplasmic reticulum; GCN2: general control nonderepressible 2; IL: interleukin; KCNK3: potassium two pore domain channel subfamily K member 3; PVOD: pulmonary veno-occlusive disease; TGF-β: transforming growth factor-β.

Controversies and consequences of pulmonary arterial hypertension therapy.