G-CSF induced arteriogenesis in humans: molecular insights into a randomized controlled trial

Meier, Pascal; Glökler, Steffen; Oezdemir, Berna; Indermuehle, Andreas; Traupe, Tobias; Vogel, Rolf; de Marchi, Stefano; Seiler, Christian (2013). G-CSF induced arteriogenesis in humans: molecular insights into a randomized controlled trial. Current vascular pharmacology, 11(1), pp. 38-46. Bentham Science Publishers 10.2174/157016113804547674

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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 (10 μg/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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Glökler, Steffen; Traupe, Tobias; de Marchi, Stefano and Seiler, Christian

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1570-1611

Publisher:

Bentham Science Publishers

Language:

English

Submitter:

PD Dr. Tobias Traupe

Date Deposited:

19 Mar 2014 13:42

Last Modified:

19 Mar 2014 13:42

Publisher DOI:

10.2174/157016113804547674

PubMed ID:

23391421

URI:

https://boris.unibe.ch/id/eprint/43356

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