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Innovation thérapeutique dans la dysfonction endothéliale associée à l'hypertension artérielle pulmonaire

Abstract : Pulmonary arterial hypertension (PAH) is a severe disease characterized by progressive obstruction of small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance and to right heart failure and death. Vasoconstriction, pulmonary vascular remodeling, in situ thrombosis and endothelial dysfunction are all factors that contribute to the development and progression of the disease. These work aimed to clarify and better understand the abnormal phenotype of the pulmonary endothelial cell (P-EC) of PAH patients to identify new therapeutic targets to correct and restore the endothelial dysfunction associated with pulmonary hypertension. Several functional disturbances related to molecular abnormalities have been identified. The IPAH-P-EC is characterized by proliferation, migration, survival and an excessive response to various growth factors: PDGF, EGF, and FGF2. Among the molecular abnormalities responsible for these functional disturbances, we found an abnormal production and release of FGF2, MMP2, MIF, IL-6 and MCP-1, but also a constitutive activity of MAPK, overexpression of anti-apoptotic factors BCL2 and BCL-xL, of FGFR2, of p130Cas and CD74. This better understanding of the EC-IPAH has already identified several targets that could be evaluated and also helped raise a number of issues requiring further study.
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  • HAL Id : tel-00923004, version 1

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Ly Tu. Innovation thérapeutique dans la dysfonction endothéliale associée à l'hypertension artérielle pulmonaire. Médecine humaine et pathologie. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA114823⟩. ⟨tel-00923004⟩

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