The Effect of Intracoronary Stem Cell Injection on Markers of Leukocyte Activation in Acute Myocardial Infarction

Ragnhild Helseth; Trine Opstad; Svein Solheim; Ketil Lunde; Harald Arnesen; Ingebjorg Seljeflot

doi:10.14740/cr375w

The Effect of Intracoronary Stem Cell Injection on Markers of Leukocyte Activation in Acute Myocardial Infarction

Cardiol Res. 2015 Feb;6(1):209-215. doi: 10.14740/cr375w. Epub 2015 Feb 9.

Authors

Ragnhild Helseth¹, Trine Opstad¹, Svein Solheim², Ketil Lunde³, Harald Arnesen¹, Ingebjorg Seljeflot¹

Affiliations

¹ Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
² Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway.
³ Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

PMID: 28197227
PMCID: PMC5295555
DOI: 10.14740/cr375w

Abstract

Background: Beneficial effects of stem cell treatment during acute myocardial infarction (AMI) have been suggested, but the effects on inflammation are controversial. The neutrophil cell markers pentraxin 3 (PTX3) and myeloperoxidase (MPO) are both reported to be elevated during AMI. We studied the effects of stem cell treatment in ST-elevation myocardial infarction (STEMI) on PTX3 and MPO levels.

Methods: Subjects with STEMI undergoing percutaneous coronary intervention (PCI) were randomized to intracoronary injection of bone marrow cells (mBMCs) (n = 50) or controls (n = 50). Blood samples were drawn 1 day before mBMC injection (baseline), after 1 day, 3 days, 2 - 3 weeks and 3 months. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used for biochemical analysis. Myocardial necrosis was quantified by single photon emission computed tomography (SPECT) and creatine kinase MB (CKMB) levels.

Results: PTX3 and MPO levels did not differ between the groups at any time points. Within the mBMC group, overall changes in both variables were observed (P < 0.01), with decreased levels from baseline throughout. Within the control group, similar patterns were observed. The relative reduction of PTX3 from baseline to day 1 was significantly less pronounced in the mBMC group compared to controls (P = 0.002), whereas no differences in relative changes from baseline were observed for MPO. Plasma and gene expression levels of PTX3 in leukocytes correlated significantly at all time points (r = 0.379 - 0.448, P < 0.01, all). MPO was significantly correlated to baseline left ventricular ejection fraction (LVEF) (r = -0.229, P = 0.025) and peak CKMB (r = 0.200, P = 0.05).

Conclusions: Stem cell treatment had limited effect on plasma levels of PTX3 and MPO. The initially high PTX3 and MPO levels, the genetic regulation of PTX3 and the association between MPO and myocardial injury support the importance of neutrophil cell activation in STEMI.

Keywords: Acute myocardial infarction; Bone marrow stem cells; Myeloperoxidase; Neutrophil markers; Pentraxin 3; Stem cell treatment.