Smooth muscle cell matrix metalloproteinases in idiopathic pulmonary arterial hypertension
| Autor: | Saadia Eddahibi, Marc Humbert, Marie Pia d'Ortho, H. Lepetit, E. Fadel, Serge Adnot, C. Lafuma, Agnès Noël, Carine Munaut, Eric Frisdal |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Matrix Metalloproteinases Membrane-Associated Smooth muscle cell migration Hypertension Pulmonary Myocytes Smooth Muscle Matrix metalloproteinase Vascular remodelling in the embryo Extracellular matrix Reference Values medicine Humans Myocyte Cells Cultured Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 business.industry Respiratory disease Metalloendopeptidases medicine.disease Pulmonary hypertension Matrix Metalloproteinases medicine.anatomical_structure Matrix Metalloproteinase 9 Matrix Metalloproteinase 7 Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Matrix Metalloproteinase 1 business Artery |
| Zdroj: | European Respiratory Journal. 25:834-842 |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.05.00072504 |
| Popis: | Pulmonary arterial hypertension (PAH) results from persistent vasoconstriction, smooth muscle growth and extracellular matrix (ECM) remodelling of pulmonary arteries (PAs). Matrix metalloproteinases (MMPs) are matrix-degrading enzymes involved in ECM turnover, and in smooth muscle cell (SMC) and endothelial cell migration and proliferation. MMP expression and activity are increased in experimental PAH. Therefore, this study investigated whether similar changes occur in idiopathic PAH (IPAH; formerly known as primary pulmonary hypertension). Both in situ and in vitro studies were performed on PAs from patients undergoing lung transplantation for IPAH and from patients treated by lobectomy for localised lung cancer, who served as controls. In IPAH, MMP-tissue inhibitor of metalloproteinase (TIMP) imbalance was found in cultured PA-SMCs, with increased TIMP-1 and decreased MMP-3. MMP-2 activity was markedly elevated as a result of increases in both total MMP-2 and proportion of active MMP-2. In situ zymography and immunolocalisation showed that MMP-2 was associated with SMCs and elastic fibres, and also confirmed the MMP-3-TIMP-1 imbalance. In conclusion, the findings of this study were consistent with a role for the matrix metalloproteinase-tissue inhibitor of metalloproteinase system in pulmonary vascular remodelling in idiopathic pulmonary arterial hypertension. The matrix metalloproteinase-tissue inhibitor of metalloproteinase imbalance may lead to matrix accumulation, and increased matrix metalloproteinase-2 activity may contribute to smooth muscle cell migration and proliferation. Whether these abnormalities are potential therapeutic targets deserves further investigation. |
| Databáze: | OpenAIRE |
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