Serum matrix metalloproteinases and left atrial remodeling—the Hoorn study

Pauline B.C. Linssen, Hans Peter Brunner-La Rocca, Casper G. Schalkwijk, Joline W.J. Beulens, Petra J.M. Elders, Amber A. van der Heijden, Roderick C. Slieker, Coen D.A. Stehouwer, Ronald M.A. Henry

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Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n = 674), underwent echocardiography. Serum MMPs (i.e. MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; −0.04 (−0.07; −0.01) and −0.04 (−0.06; −0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07, p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; −0.05 (−0.09; −0.01, p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex.

Original languageEnglish
Article number4944
Pages (from-to)1-11
Number of pages11
JournalInternational journal of molecular sciences
Issue number14
Publication statusPublished - 2 Jul 2020


  • Diastolic dysfunction
  • Echocardiography
  • LA-volume index
  • Matrix metalloproteinase (MMPs)
  • Tissue inhibitor of matrix metalloproteinases (TIMP-1)

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