Circulating biomarkers of tissue remodelling in pulmonary hypertension

Abstract

Objective: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role.

Methods: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed.

Results: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy.

Conclusion: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Keywords::

• Biomarkers
• tissue remodelling
• pulmonary hypertension
• matrix metalloproteinase 2
• tenascin C
• tissue inhibitor of matrix metalloproteinase 4

Acknowledgements

The authors thank Markus Keil and Martin Kretz for excellent technical assistance.

Declaration of interest

F.K. and T.K. are full time employees of Bayer HealthCare AG, Germany. C.S. received research grants from Bayer HealthCare AG in 2008.