Human pulmonary arterial hypertensionDrapeau Français

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.

équipe 1 axe 3 fig Thème 2A 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.

Collaborations :

  •  Service de Chirurgie Thoracique (Pr Elie Fadel, Hôpital Marie Lannelongue, Ile de France).

Major Publications :

Coordinator :

 Participant :

Richard Sylvain