Table 1.
Pathogenetic mechanisms of pulmonary hypertension associated with interstitial lung disease.
| Citation | Model | Findings |
|---|---|---|
| Disequilibrium of pro‐ and antiangiogenic pathways | ||
| Ruffenach et al. 12 | Murine model of PH‐PF | ↑ Vascular wall thickness in fibrotic and nonfibrotic areas of PH‐PF patient lungs compared to non‐PH‐PF patients. Role of macrophages and Slug/PIP axis |
| Farkas et al. 25 | Murine model of PF overexpressing TGFβ1 | ↓ Expression of VEGF, increased cell apoptosis, ↓ vascular density. Replacement of VEGF: ↑fibrosis |
| Wu et al. 14 | Human lung tissue and murine bleomycin‐monocrotaline model | ↑ Activation and expression of checkpoint kinases 1/2 in fibroblast and PASMC: proliferative and apoptosis‐resistant endophenotype. Reversible after inhibition |
| Lambers et al. 15 | Murine model of PF | Antifibrotic action of treprostinil. ↓ Recruitment of fibrocyte to sites of vascular remodeling |
| Molecular and genetic abnormalities | ||
| Mura et al. 16 | Human lung tissue: microarray gene expression | NoPH‐PF: proinflammatory gene signature, PH‐PF: pro‐proliferative gene signature |
| Chen et al. 17 | Human lung tissue | ↓ Expression of BMPR2 isoform A in macrophages and PASMC of IPF and IPF‐PH versus normal lung samples. Different miRNA profile |
| Jiang et al. 18 | Murine bleomycin model | ↓ Expression of the BMP9/BMP2/SMAD pathway. Regression of lesions after recombinant BMPR9 |
| Thoré et al. 19 Hernandez‐González et al. 20 | Human PAH families | TBX4 mutation in patients with PAH and ILD, small patella syndrome, and congenital heart disease |
| Eyries et al. 21 | Human PAH families | KDR mutations associated with PAH and ILD |
Abbreviations: BMP2, bone morphogenetic protein 2; BMP9, bone morphogenetic protein 9; BMPR2, bone morphogenetic protein receptor type‐2; ILD, interstitial lung disease; IPF, idiopatic pulmonary fibrosis; IPF‐PH, idiopathic pulmonary fibrosis with pulmonary hypertension; KDR, kinase insert domain receptor gene; NoPH‐PF, pulmonary fibrosis without pulmonary hypertension; PAH, pulmonary arterial hypertension; PASMC, pulmonary arterial smooth muscle cells; PH, pulmonary hypertension; PH‐PF, pulmonary fibrosis with pulmonary hypertension; PIP, prolactin‐induced protein; TBX4, T‐box transcription factor 4; TGF1 β, transforming growth factor β1; VEGF, vascular endothelial growth factor.