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Angiogenesis

, Volume 19, Issue 1, pp 67–78 | Cite as

Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia

  • Jörn F. DopheideEmail author
  • Philipp Geissler
  • Jennifer Rubrech
  • Amelie Trumpp
  • Geraldine C. Zeller
  • Karsten Bock
  • Bernhard Dorweiler
  • Friedrich Dünschede
  • Thomas Münzel
  • Markus P. Radsak
  • Christine Espinola-Klein
Original Paper

Abstract

Background

Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells.

Methods

Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months.

Results

In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01).

Conclusions

We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.

Keywords

EPC TEM Peripheral arterial disease Critical limb ischemia Inflammation 

Notes

Acknowledgments

This paper contains in part data reported in the medical thesis of Jennifer Rubrech, Amelie Trumpp, and Philip Geissler. The authors like to thank Ursel Petrat, Sabine Wolk, and Andrea Drescher for excellent technical support.

Compliance with ethical standards

Conflict of interest

All authors declare that there is no conflict of interest.

Supplementary material

10456_2015_9489_MOESM1_ESM.pdf (42 kb)
Supplementary material 1 (PDF 42 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Jörn F. Dopheide
    • 1
    Email author
  • Philipp Geissler
    • 1
  • Jennifer Rubrech
    • 1
  • Amelie Trumpp
    • 1
  • Geraldine C. Zeller
    • 2
  • Karsten Bock
    • 1
  • Bernhard Dorweiler
    • 5
  • Friedrich Dünschede
    • 5
  • Thomas Münzel
    • 1
  • Markus P. Radsak
    • 3
    • 4
  • Christine Espinola-Klein
    • 1
  1. 1.Department of Internal Medicine IIUniversity Medical Center, Johannes Gutenberg-University MainzMainzGermany
  2. 2.Department of Internal Medicine IUniversity Medical Center, Johannes Gutenberg-University MainzMainzGermany
  3. 3.Department of Internal Medicine IIIUniversity Medical Center, Johannes Gutenberg-University MainzMainzGermany
  4. 4.Institute for ImmunologyUniversity Medical Center, Johannes Gutenberg UniversityMainzGermany
  5. 5.Division of Vascular Surgery, Department of Cardiothoracic and Vascular SurgeryUniversity Medical Center, Johannes-Gutenberg UniversityMainzGermany

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