Heparin affects matrix metalloproteinases and tissue inhibitors of metalloproteinases circulating in peripheral blood

Objectives: Blood sampling/handling alters matrix metalloproteinases (MMP) and tissue inhibitor (TIMP) expression. The aim of this study is to evaluate the effects of high molecular weight heparin on MIMP and TIMP expression in blood. Design and methods: We analyzed by gelatin zymography and ELISA assays the effects of different heparin salts, dose- and time-dependence of MMP and TIMP concentrations in plasma and sera collected with and without clot-accelerator in plastic tubes From 50 healthy donors. Results: The levels and zymography of MMP-2 did not show significant changes among all samples, and during time- and dose-dependent heparin treatments. MMP-9 and TIMP-2 expression were strongly affected by heparin, with significant increase of their content and gelatinolytic activity both in time- and in dose-dependent fashion. Addition of heparin allowed also the displacement of MMP-2 prodomain, favoring zymogen activation. Conclusions: Heparin has direct and indirect effects, altering MMP/TIMP complexes circulating in blood, and increasing the release of TIMP-2. To avoid misinterpretations due to MMP/TIMP complex alteration and MMP prodomain displacement, heparin should be cautiously used in blood collection procedures. (c) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.