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.

MMP-9 and Its Regulators TIMP-1 and EMMPRIN in Patients with Acute ST-Elevation Myocardial Infarction: A NORDISTEMI Substudy

“…All 3 markers declined significantly after the acute initial event, which is in line with previous observations [4,17]. The high circulating levels measured on day 3 were probably due to acute-phase processes.…”

“…However, we have previously shown that expression of the EMMPRIN gene in circulating leukocytes correlated with myocardial injury, as measured by creatine kinase and SPECT-based infarct size in another group of STEMI patients [17]. As reports on EMMPRIN in this context are limited [26] and are mostly restricted to in vitro animal models, further exploration is warranted.…”

Plasma EMMPRIN levels in acute myocardial infarction and stable coronary artery disease

“…It has also been reported that in AMI patients, soluble EMMPRIN is positively correlated with infarct size, measured by single-photon emission tomography and peak CK, and inversely correlated with LVEF [34]. It can be concluded that these results, and our results demontrating that EMMPRIN is significantly positively correlated with peak CK-MB and peak cTnT, inversely correlated with LVEF, are in favour of the notion that EMMPRIN is a causative factor in AMI.…”

“…Knowledge on the temporal changes in EMMPRIN in AMI is limited, with only two published studies [14,34] on this matter. One study [14] reported that the expression level of EMMPRIN on monocytes was significantly elevated in AMI patients whose onset of chest pain was >24 hours previously, than in those whose onset of chest pain was <24 hours.…”

“…One study [14] reported that the expression level of EMMPRIN on monocytes was significantly elevated in AMI patients whose onset of chest pain was >24 hours previously, than in those whose onset of chest pain was <24 hours. In the other study [34], the baseline levels of circulating soluble EMMPRIN were determined median one day following chest pain onset, and these levels were significantly reduced after two to three weeks. In our study, blood was sampled 4.5±3.4 and 5.2±3.3 hours after chest pain onset in the STEMI and NSTEMI patients, respectively.…”