European Respiratory Society

Matrix metalloproteinases and their inhibitors in pulmonary hypertension

Prakash Chelladurai, Werner Seeger, Soni Savai Pullamsetti


Pulmonary hypertension (PH) is a severe and progressive disease characterised by high pulmonary artery pressure, usually culminating in right heart failure. Current therapeutic approaches in PH largely provide symptomatic relief while the prognosis rate is lower due to the lack of specific molecular targets and the involvement of several factors in the development of PH. Numerous studies have suggested a crucial role of matrix metalloproteinase (MMP) axis during development and disease states, specifically with regard to extracellular matrix remodelling and vascular homeostasis. Increased MMP activity has been demonstrated in experimental animal models of PH, and MMP inhibition has been shown to either attenuate or enhance vascular remodelling. Moreover, several studies emphasise that restoration of deregulated MMPs to physiological MMP/tissue inhibitor of MMPs ratios would potentiate reverse remodelling in PH. This article will highlight the pathophysiological role of MMPs in vascular remodelling and the establishment of PH. In particular, we will focus on the MMP expression and regulation in pulmonary vasculature and pulmonary vascular remodelling. We will also provide an overview of recent clinical and experimental findings and their impact on achieving maximum reversal of PH, as well as current issues and future perspectives.


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  • Previous articles in this series. No. 1: Löffek S, Schilling O, Franzke C-W. Biological role of matrix metalloproteinases: a critical balance. Eur Respir J 2011; 38: 191–208. No. 2: Elkington PT, Ugarte-Gil CA, Friedland JS. Matrix metalloproteinases in tuberculosis. Eur Respir J 2011; 38: 456–464. No. 3: Gaggar A, Hector A, Bratcher PE, et al. The role of matrix metalloproteinases in cystic fibrosis lung disease. Eur Respir J 2011; 38: 721–727. No. 4: Davey A, McAuley DF, O’Kane CM. Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair. Eur Respir J 2011; 38: 959–970. No. 5: Vandenbroucke RE, Dejonckheere R, Libert C. A therapeutic role for matrix metalloproteinase inhibitors in lung diseases? Eur Respir J 2011; 38: 1200–1214. No. 6: Dancer RCA, Wood AM, Thickett DR. Metalloproteinases in idiopathic pulmonary fibrosis. Eur Respir J 2011; 38: 1461–1467. No. 7: Churg A, Zhou S, Wright JL. Matrix metalloproteinases in COPD. Eur Respir J 2012; 39: 197–209. No. 8: Dagouassat M, Lanone S, Boczkowski J. Interaction of matrix metalloproteinases with pulmonary pollutants. Eur Respir J 2012; 39: 1021–1032.

  • Statement of Interest

    None declared.

  • Received November 30, 2011.
  • Accepted April 3, 2012.
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