Table 1.
Transcription factors in PH
| Gene | Full name | Role in PH | Cells/tissue samples investigated in PH | References |
|---|---|---|---|---|
| PPARG1 | Peroxisome proliferator–activated receptor γ | Decreased expression in PH; PPARγ agonists might reverse pulmonary vascular remodeling | IPAH lungs, SuHx-PH | Ameshima et al.;14 Hansmann et al.15 |
| HIF2A | Hypoxia-inducible factor 2α | Hif2a/Epas1 heterozygous mice were fully protected against PH and RVH; HIF2A-mediated upregulation of vasoconstrictors contributes to the development of hypoxic PH | Rodent HPH | Brusselmans et al.16 |
| HIF1A | Hypoxia-inducible factor 1α | Normoxic HIF activation in FHR and human PAs from IPAH; partial deficiency of either HIF1α- or HIF2α-attenuated PAP and RVH | Rodent HPH, FHR-PH, IPAH PASMCs | Bonnet et al.17 |
| NFATc2 | Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 | Activated in CD3+ lymphocytes; NFAT inhibition reverses MCT-induced established PAH | IPAH PASMCs MCT-PH | Bonnet et al.18 |
| STAT3 | Signal transducers and activators of transcription 3 | Persistent activation of STAT3 was identified in IPAH PAECs | IPAH | Masri et al.19 |
| HES5 | Hes family bHLH transcription factor 5 | High levels of HES5 in lung tissue correlated with worsening disease severity | IPAH, rodent HPH | Li et al.20 |
| Smad8/Smad9 | Mothers against decapentaplegic homolog 8 | Abnormal vascular remodeling in Smad8 mutants | Transgenic | Huang et al.21 |
| OCT4 | Octamer-binding transcription factor 4 | OCT4 isoforms were upregulated in PASMCs from human PAH | IPAH PASMCs | Firth et al.22 |
| NFATc3 | Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 | Activated in neonatal mice exposed to chronic hypoxia; Nfatc3 KO mice do not show PA remodeling | Rodent HPH | Bierer et al.23 |
| KLF5 | Krüppel-like factor 5 | KLF5 is upregulated in human and MCT-induced PAH | IPAH lungs and PASMCs | Courboulin et al.24 |
| P53 | Tumor protein p53 | Gene deficiency promotes HPH and vascular remodeling | Rodent HPH | Mizuno et al.25 |
| Lef1 | Lymphoid enhancer factor 1 | Upregulated in HPH in neonatal rats | Rodent HPH | Xu et al.26 |
| PPARGC1A (PGC-1α) | Peroxisome proliferator-activated receptor gamma coactivator 1α | Upregulated mRNA expression | IPAH blood samples | Mata et al.27 |
| NF-KB/RELA | Nuclear factor κ-B | NF-κB is activated in pulmonary macrophages, lymphocytes, endothelial cells, and PASMCs | IPAH | Price et al.28 |
| GATA6 | GATA-binding protein 6 | Endothelial GATA-6 deficiency promotes PAH | SSc-PAH, IPAH | Ghatnekar et al.29 |
| c-JUN, c-FOS | Jun proto-oncogene, FBJ murine osteosarcoma viral oncogene homolog | Higher levels of total and phosphorylated c-JUN and c-FOS in the vessel wall | IPAH lungs | Biasin et al.30 |
| FOXO1 | Forkhead box O1 | FOXO1 expression is downregulated and inactivated; FOXO1 activation reverses the development of PH | IPAH, MCT-PH, SuHx-PH | Savai et al.31 |
| KLF4 | Krüppel-like factor 4 | KLF4 gene and protein expression is reduced in lungs from patients with PAH; loss of endothelial KLF4 exacerbates pulmonary vessel muscularization | IPAH lungs | Shatat et al.32 |
| MEF2 | Myocyte enhancer factor 2 | MEF2 transcriptional activity is impaired | IPAH/FPAH PAECs | Kim et al.33 |
| TWIST1 | Twist family bHLH transcription factor 1 | EndoMT; neointimal and plexiform lesion formation; role in neomuscularization | PAH, MCT-PH, SuHx-PH, Bmpr2+/− rats | Ranchoux et al.34 |
| SLUG | Snail family zinc finger 2 | EndoMT | BMPR2 KO PAECs | Hopper et al.35 |
Note
bHLH: basic helix-loop-helix; EndoMT: endothelial-to-mesenchymal transition; FHR: fawn-hooded rat; HPH: hypoxia-induced PH; IPAH: idiopathic PAH; KO: knockout; MCT-PH: monocrotaline-induced PH; mRNA: messenger RNA; PA: pulmonary artery; PAECs: pulmonary arterial endothelial cells; PAH: pulmonary arterial hypertension; PAP: pulmonary artery pressure; PASMCs: pulmonary artery smooth muscle cells; PH: pulmonary hypertension; RVH: right ventricular hypertrophy; SSc-PAH: systemic sclerosis–associated PAH; SuHX-PH: hypoxia+SU5416–induced PAH (SU5416 is a vascular endothelial growth factor receptor [VEGFR-2] inhibitor).