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Shockwave Therapy Differentially Stimulates Endothelial Cells: Implications on the Control of Inflammation via Toll-Like Receptor 3

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Abstract

Shock wave therapy (SWT) reportedly improves ventricular function in ischemic heart failure. Angiogenesis and inflammation modulatory effects were described. However, the mechanism remains largely unknown. We hypothesized that SWT modulates inflammation via toll-like receptor 3 (TLR3) through the release of cytosolic RNA. SWT was applied to human umbilical vein endothelial cells (HUVECs) with 250 impulses, 0.08 mJ/mm2 and 3 Hz. Gene expression of TLR3, inflammatory genes and signalling molecules was analysed at different time points by real-time polymerase chain reaction. SWT showed activation of HUVECs: enhanced expression of TLR3 and of the transporter protein for nucleic acids cyclophilin B, of pro-inflammatory cytokines cyclophilin A and interleukin-6 and of anti-inflammatory interleukin-10. No changes were found in the expression of vascular endothelial cell adhesion molecule. SWT modulates inflammation via the TLR3 pathway. The interaction between interleukin (IL)-6 and IL-10 in TLR3 stimulation can be schematically seen as a three-phase regulation over time.

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Abbreviations

CYP:

Cyclophilin

DNA:

Deoxyribonucleic acid

dsRNA:

Double-stranded ribonucleic acid

HUVEC:

Human umbilical vein endothelial cell

IL:

Interleukin

PCR:

Polymerase chain reaction

Poly(I:C):

Polyinosinic:polycytidylic acid

Tie2:

Tyrosine kinase with immunoglobulin-like and EGF-like domains 2

TLR3:

Toll-like receptor 3

VCAM:

Vascular endothelial cell adhesion molecule

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Acknowledgments

This work was in part funded by a research grant from Bayer Pharma AG (Grants4Targets) to P.P. and by Medizinischer Forschungsfonds Tirol (MFF) project no. 220 to J.H. The sponsors of this study had no role in study design, data collection, analysis, and decision to publish or prepare the manuscript nor have any financial interest.

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Holfeld, J., Tepeköylü, C., Kozaryn, R. et al. Shockwave Therapy Differentially Stimulates Endothelial Cells: Implications on the Control of Inflammation via Toll-Like Receptor 3. Inflammation 37, 65–70 (2014). https://doi.org/10.1007/s10753-013-9712-1

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