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MMPs, inflammation and pulmonary arterial hypertension

  • Marie-Pia d’Ortho
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Pulmonary arterial hypertension (PAH) is characterised by remodelling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure [1]. PAH can be idiopathic, familial, or associated with a number of conditions or diseases, such as connective tissue disease. Its prognosis is poor, less than 3 yr from diagnosis. The aetiology of severe unexplained pulmonary hypertension remained largely unknown until a few years ago. The gene underlying familial PAH was identified in 2000, the BMPR-2 gene. However its mutations are not always present, and it probably does not explained the full scope of the disease. PAH is associated with structural alterations in pulmonary arteries including intimal fibrosis, medial hypertrophy and adventitial changes, pointing towards extracellular matrix remodelling which have raised the question of involvement of the matrix degrading enzymes. Among them, serine proteases, such as plasmina and endogenous vascular elastase (EVE), and matrix metalloproteases have been studied. In experimental models, the three of them are increased. Accordingly, their inhibition has preventing and in some cases therapeutic effects. However it should be stressed that opposite consequence of protease inhibition on PAH can be observed depending on the experimental model, either chronic hypoxia-induced PAH (deleterious) or toxic moncrotalin-induced PAH (positive). In humans, only sparse reports exist, that found increase in the MMP inhibitor, TIMP-1, and MMP-2 expression and decreased collagenase (MMP-1). Inflammation is part of the PAH, and accordingly, protease production is a well known part of the inflammatory response. Answering the question whether protease inhibition might represent a therapeutic option in human PAH is however certainly too early.

Keywords

Pulmonary Hypertension Pulmonary Arterial Hypertension Idiopathic Pulmonary Arterial Hypertension Pulmonary Artery Smooth Muscle Cell Smooth Muscle Cell Migration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Marie-Pia d’Ortho
    • 1
    • 2
    • 3
  1. 1.Unité U841, IRBM, Département Foie-Coeur-Poumon, équipe 6INSERMFrance
  2. 2.Faculté de Médecine, IFR10Université Paris 12France
  3. 3.AP-HP, Groupe Henri Mondor — Albert ChennevierService de Physiologie — Explorations FonctionnellesCréteilFrance

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