G-CSF Induced Arteriogenesis in Humans: Molecular Insights into a Randomized Controlled Trial

Author(s): Pascal Meier, Steffen Gloekler, Berna Oezdemir, Andreas Indermuehle, Tobias Traupe, Rolf Vogel, Stefano de Marchi, Christian Seiler.

Journal Name: Current Vascular Pharmacology

Volume 11 , Issue 1 , 2013

Abstract:

Aims: Recent data have demonstrated the feasibility of therapeutic induction of coronary collateral growth (arteriogenesis); however, mechanisms of action of such therapeutic collateral stimulation in humans are unknown. The aim of this study was to evaluate potential mechanisms, especially the involvement of arteriogenesis-relevant genes. Methods and Results: A total of 52 patients were randomized into two groups: subcutaneous G-CSF (10μg/kg; n=26) or placebo (n=26). Before and after this 2-week treatment, collateral-flow index (CFI) was determined by simultaneous measurement of mean aortic, distal coronary occlusive and central venous pressure. CD34+ endothelial progenitor cells (EPC) and monocytes were quantified before, during and after treatment; gene-expression analysis of monocytes was performed with real-time polymerase chain reaction (RT-PCR). G-CSF lead to a significant increase of EPC and monocytes (4.8 and 2.6 fold, p<0.05); for both cell types, the extent of increase correlated with CFI increase (r=0.23 and 0.14, p<0.05). G-CSF also induced a change in gene expression of pro-and anti-arteriogenic genes in monocytes. Among nine assessed genes, three were found to be differentially regulated (IL8, JAK2, and PNPLa4; p<0.05). Conclusions: The mechanism of induction of collateral growth by G-CSF is related to an increase of EPC and of peripheral monocytes. It also leads to a change toward a pro-arteriogenic gene expression in peripheral monocytes.

Keywords: Arteriogenesis, collateral circulation, granulocyte-colony stimulating factor, endothelial progenitor cells, monocytes, gene expression

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Article Details

VOLUME: 11
ISSUE: 1
Year: 2013
Page: [38 - 46]
Pages: 9
DOI: 10.2174/1570161111309010038

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