The influence of autologous bone marrow stem cell transplantation on matrix metalloproteinases in patients treated for acute ST-elevation myocardial infarction

Abstract

Background: Matrix metalloproteinase-9 (MMP-9), regulated by tissue inhibitor of metalloproteinase-9 (TIMP-1) and the extracellular matrix metalloproteinase inducer (EMMPRIN), contributes to plaque instability. Autologous stem cells from bone marrow (mBMC) treatment are suggested to reduce myocardial damage; however, limited data exists on the influence of mBMC on MMPs.

Aim: We investigated the influence of mBMC on circulating levels of MMP-9, TIMP-1, and EMMPRIN at different time points in patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial (n = 100). Gene expression analyses were additionally performed.

Results: After 2-3 weeks we observed a more pronounced increase in MMP-9 levels in the mBMC group, compared to controls (P = 0.030), whereas EMMPRIN levels were reduced from baseline to 2-3 weeks and 3 months in both groups (P < 0.0001). Gene expression of both MMP-9 and EMMPRIN was reduced from baseline to 3 months. MMP-9 and EMMPRIN were significantly correlated to myocardial injury (CK: P = 0.005 and P < 0.001, resp.) and infarct size (SPECT: P = 0.018 and P = 0.008, resp.).

Conclusion: The results indicate that the regulation of metalloproteinases is important during AMI, however, limited influenced by mBMC.

Figure 1

Gene expression of MMP-9 (a) and EMMPRIN (b) after 2-3 weeks and 3 months in the mBMC group and controls relative to baseline expression in the total population. Black bars: total group at baseline; grey bars: mBMC group; white bars: controls. ∗ indicates reduction from baseline to 3 months in the mBMC group P values refer to differences in expression relative to baseline between groups.