Idiopathic pulmonary arterial hypertension (idiopathic HTAP) is a rare, fatal, which develops in a primitive way. It is identified by an increase in pulmonary blood pressure with increased proliferation of pulmonary vascular smooth muscle cells (SMC-VP) which leads to a reduction of the vessel lumen or clogging.
A breakthrough in our understanding of the molecular and cellular mechanisms of (HTAPi) took place thanks to the functional and genetic studies of tissues obtained from patients carrying the disease. Thus, we have shown that SMC-VP from patients wit
h HTAPi is abnormal and has some similarities to the tumor cell (ANR 2009 GENOPAT).
Figure 1 : Alteration of intrinsic pulmonary artery smooth muscle cell properties in pulmonary hypertension
This assumption is based on the following data :
(1) SMC-VP of patients with idiopathic HTAP has a great capacity for proliferation and resistance to senescence associated with telomere stability;
(2) as in tumor cells, we have demonstrated an alteration of the TGF-β pathway in SMC-VP of these patients (Dewachter et al. ERJ 2009);
(3) proteomic and functional analysis of these cells shows a breakdown of the expression of p53, p21, p16 and retinoblastoma protein in HTAPi; (4) inhibition of certain tyrosine kinases so appears to be effective and offers hope for the treatment of HTAP.
- Service de Chirurgie Thoracique (Pr Elie Fadel, Hôpital Marie Lannelongue, Ile de France).
Major Publications :
- Tu L, Dewachter L, Gore B, Fadel E, Dartevelle P, Simonneau G, Humbert M, Eddahibi S, Guignabert C. Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension. Am J Respir Cell Mol Biol. 2011 ; 45(2):311-22.
- Hara Y, Sassi Y, Guibert C, Gambaryan N, Dorfmüller P, Eddahibi S, Lompré AM, Humbert M, Hulot JS. Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J Clin Invest. 2011 ; 121(7):2888-97.
- Sage E, Mercier O, Herve P, Tu L, Dartevelle P, Eddahibi S, Fadel E. Right lung ischemia induces contralateral pulmonary vasculopathy in an animal model. J Thorac Cardiovasc Surg. 2012 ; 143(4):967-73.
- De Man FS, Tu L, Handoko ML, Rain S, Ruiter G, François C, Schalij I, Dorfmüller P, Simonneau G, Fadel E, Perros F, Boonstra A, Postmus PE, van der Velden J, Vonk-Noordegraaf A, Humbert M, Eddahibi S, Guignabert C. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension.. Am J Respir Crit Care Med. 2012 ; 186(8):780-9.
- Perros F, PhD, Ranchoux B, Izikki M, Bentebbal S, Happé C, Antigny F, Jourdon P, Dorfmüller P, Lecerf F, Fadel E, Simonneau G, Humbert M, MD, Bogaard HJ, Eddahibi S. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension J Am Coll Cardiol 2014 (in press soon).
- Gore B, Izikki M, Mercier O, Dewachter L, Fadel E, Humbert M, Dartevelle P, Simonneau G, Naeije R, Lebrin F, Eddahibi S. Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension. PLoS One. 2014 ; 9(6):e100310.
- Khalifé-Hocquemiller T, Sage E, Dorfmuller P, Mussot S, Le Houérou D, Eddahibi S, Fadel E. Exogenous surfactant attenuates lung injury from gastric-acid aspiration during ex vivo reconditioning in pigs.. 2014 ; 97(4):413-8.