TY - JOUR
T1 - Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction
AU - Stein, Andreas
AU - Zohlnhöfer, Dietlind
AU - Pogatsa-Murray, Gisela
AU - Von Wedel, Jasper
AU - Steppich, Birgit A.
AU - Schömig, Albert
AU - Kastrati, Adnan
AU - Ott, Ilka
PY - 2010/3
Y1 - 2010/3
N2 - G-CSF induced mobilisation of progenitor cells is a multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on haematopoietic cells. This study's aim was to investigate progenitor cells mobilised during myocardial infarction after treatment with granulocytestimulating factor (G-CSF). In the randomised, double-blind, placebocontrolled REVIVAL-2 study, 114 patients with acute myocardial infarction were included. Five days after successful percutaneous coronary intervention patients received either 10 μg/kg G-CSF (n=56) or placebo (n=58) subcutaneously for five days. Venous blood samples were analysed on day(s) 1, 3, 5 and 7 after therapy, and progenitor cell mobilisation and surface expression of VLA-4, LFA-1 and CXCR-4 was measured on circulating progenitor cells using flow cytometry. G-CSF induced a significant increase in circulating progenitor cells (72 ± 20 cells/μl vs. 4.5 ± 0.8 cells/μl, p<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on progenitor cells was decreased by 44%, 49% and 60% after G-CSF as compared to placebo (p<0.05). In accordance, mRNA expression of CXCR4 was reduced. Moreover, anti-proliferative transducer of ERB (TOB) mRNA was decreased, suggesting an increased proliferative potential of the mobilised progenitor cells. Decreased expression of adhesion and chemokine receptors on G-CSF mobilised progenitor cells in acute myocardial infarction may alter the homing capacity of circulating cells to the myocardium.
AB - G-CSF induced mobilisation of progenitor cells is a multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on haematopoietic cells. This study's aim was to investigate progenitor cells mobilised during myocardial infarction after treatment with granulocytestimulating factor (G-CSF). In the randomised, double-blind, placebocontrolled REVIVAL-2 study, 114 patients with acute myocardial infarction were included. Five days after successful percutaneous coronary intervention patients received either 10 μg/kg G-CSF (n=56) or placebo (n=58) subcutaneously for five days. Venous blood samples were analysed on day(s) 1, 3, 5 and 7 after therapy, and progenitor cell mobilisation and surface expression of VLA-4, LFA-1 and CXCR-4 was measured on circulating progenitor cells using flow cytometry. G-CSF induced a significant increase in circulating progenitor cells (72 ± 20 cells/μl vs. 4.5 ± 0.8 cells/μl, p<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on progenitor cells was decreased by 44%, 49% and 60% after G-CSF as compared to placebo (p<0.05). In accordance, mRNA expression of CXCR4 was reduced. Moreover, anti-proliferative transducer of ERB (TOB) mRNA was decreased, suggesting an increased proliferative potential of the mobilised progenitor cells. Decreased expression of adhesion and chemokine receptors on G-CSF mobilised progenitor cells in acute myocardial infarction may alter the homing capacity of circulating cells to the myocardium.
KW - Acute myocardial infarction
KW - Adhesion receptors
KW - G-CSF
KW - Progenitor cells
UR - http://www.scopus.com/inward/record.url?scp=77749289212&partnerID=8YFLogxK
U2 - 10.1160/TH09-09-0657
DO - 10.1160/TH09-09-0657
M3 - Article
C2 - 20076856
AN - SCOPUS:77749289212
SN - 0340-6245
VL - 103
SP - 638
EP - 643
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 3
ER -