M. Humbert, C. Guignabert, and S. Bonnet, Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives, Eur Respir J, vol.53, p.1801887, 2019.

R. D. Machado, L. Southgate, and C. A. Eichstaedt, Pulmonary arterial hypertension: a current perspective on established and emerging molecular genetic defects, Hum Mutat, vol.36, pp.1113-1127, 2015.

M. Eyries, D. Montani, and S. Nadaud, Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases, Eur Respir J, vol.53, p.1801371, 2019.

W. S. Kerstjens-frederikse, E. Bongers, and M. Roofthooft, TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension, J Med Genet, vol.50, pp.500-506, 2013.

M. Levy, M. Eyries, and I. Szezepanski, Genetic analyses in a cohort of children with pulmonary hypertension, Eur Respir J, vol.48, pp.1118-1126, 2016.

S. Gräf, M. Haimel, and M. Bleda, Identification of rare sequence variation underlying heritable pulmonary arterial hypertension, Nat Commun, vol.9, p.1416, 2018.

L. Ma, D. Roman-campos, and E. D. Austin, A novel channelopathy in pulmonary arterial hypertension, N Engl J Med, vol.369, pp.351-361, 2013.

E. D. Austin, L. Ma, and C. Leduc, Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension, Circ Cardiovasc Genet, vol.5, pp.336-343, 2012.

G. Wang, R. Fan, and R. Ji, Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report, BMC Pulm Med, vol.16, p.17, 2016.

N. W. Morrell, M. A. Aldred, and W. K. Chung, Genetics and genomics of pulmonary arterial hypertension, Eur Respir J, vol.53, p.1801899, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02137830

X. Wang, T. Lian, and X. Jiang, Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension, Eur Respir J, vol.53, p.1801609, 2019.

N. Ferrara, Vascular endothelial growth factor: basic science and clinical progress, Endocr Rev, vol.25, pp.581-611, 2004.

W. Liao, L. Feng, and J. Zheng, Deciphering mechanisms controlling placental artery endothelial cell migration stimulated by vascular endothelial growth factor, Endocrinology, vol.151, pp.3432-3444, 2010.

N. F. Voelkel, R. W. Vandivier, and R. M. Tuder, Vascular endothelial growth factor in the lung, Am J Physiol Lung Cell Mol Physiol, vol.290, pp.209-221, 2006.

M. Jakkula, L. Cras, T. D. Gebb, and S. , Inhibition of angiogenesis decreases alveolarization in the developing rat lung, Am J Physiol Lung Cell Mol Physiol, vol.279, pp.600-607, 2000.

L. Taraseviciene-stewart, Y. Kasahara, and L. Alger, Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension, Faseb J, vol.15, pp.427-438, 2001.

S. Richards, N. Aziz, and S. Bale, ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genet Med, vol.17, pp.405-424, 2015.

B. I. Terman, M. Dougher-vermazen, and M. E. Carrion, Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor, Biochem Biophys Res Commun, vol.187, pp.1579-1586, 1992.

T. Takahashi, S. Yamaguchi, and K. Chida, A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells, EMBO J, vol.20, pp.2768-2778, 2001.

A. Shinkai, M. Ito, and H. Anazawa, Mapping of the sites involved in ligand association and dissociation at the extracellular domain of the kinase insert domain-containing receptor for vascular endothelial growth factor, J Biol Chem, vol.273, pp.31283-31288, 1998.

H. V. Firth, S. M. Richards, and A. P. Bevan, DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources, Am J Hum Genet, vol.84, pp.524-533, 2009.

M. Lek, K. J. Karczewski, and E. V. Minikel, Analysis of protein-coding genetic variation in 60,706 humans, Nature, vol.536, pp.285-291, 2016.

E. M. Swietlik, D. Greene, and N. Zhu, Reduced transfer coefficient of carbon monoxide in pulmonary arterial hypertension implicates rare protein-truncating variants in KDR, bioRxiv, 2019.

A. Kaipainen, J. Korhonen, and K. Pajusola, The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells, J Exp Med, vol.178, pp.2077-2088, 1993.

F. Shalaby, J. Ho, and W. L. Stanford, A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis, Cell, vol.89, pp.981-990, 1997.

A. M. Healy, L. Morgenthau, and X. Zhu, VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung, Dev Dyn, vol.219, pp.341-352, 2000.

S. A. Gebb and J. M. Shannon, Tissue interactions mediate early events in pulmonary vasculogenesis, Dev Dyn, vol.217, pp.159-169, 2000.

S. H. Mitchell and W. G. Teague, Reduced gas transfer at rest and during exercise in school-age survivors of bronchopulmonary dysplasia, Am J Respir Crit Care Med, vol.157, pp.1406-1412, 1998.

Y. Kasahara, R. M. Tuder, and L. Taraseviciene-stewart, Inhibition of VEGF receptors causes lung cell apoptosis and emphysema, J Clin Invest, vol.106, pp.1311-1319, 2000.

B. Kojonazarov, S. Hadzic, and H. A. Ghofrani, Severe emphysema in the SU5416/hypoxia rat model of pulmonary hypertension, Am J Respir Crit Care Med, vol.200, pp.515-518, 2019.

R. D. Machado, M. W. Pauciulo, and J. R. Thomson, BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension, Am J Hum Genet, vol.68, pp.92-102, 2001.

M. Thirunavukkarasu, S. Addya, and B. Juhasz, Heterozygous disruption of Flk-1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis, J Cell Mol Med, vol.12, pp.1284-1302, 2008.

S. S. Oladipupo, A. U. Kabir, and C. Smith, Impaired tumor growth and angiogenesis in mice heterozygous for Vegfr2 (Flk1), Sci Rep, vol.8, p.14724, 2018.

R. M. Tuder, M. Chacon, and L. Alger, Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis, J Pathol, vol.195, pp.367-374, 2001.


M. Toba, A. Alzoubi, and K. D. O'neill, Temporal hemodynamic and histological progression in Sugen5416/ hypoxia/normoxia-exposed pulmonary arterial hypertensive rats, Am J Physiol Heart Circ Physiol, vol.306, pp.243-250, 2014.

C. M. Happé, M. A. De-raaf, and N. Rol, Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats, Am J Physiol Lung Cell Mol Physiol, vol.310, pp.1088-1097, 2016.

J. R. Roberts, G. D. Perkins, and T. Fujisawa, Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells, Crit Care Med, vol.35, pp.2164-2170, 2007.

L. Farkas, D. Farkas, and K. Ask, VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats, J Clin Invest, vol.119, pp.1298-1311, 2009.

G. Simonneau, D. Montani, and D. S. Celermajer, Haemodynamic definitions and updated clinical classification of pulmonary hypertension, Eur Respir J, vol.53, p.1801913, 2019.