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Article

C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue

by
Philipp Götz
1,2,
Anna Braumandl
1,2,
Matthias Kübler
1,2,
Konda Kumaraswami
1,2,
Hellen Ishikawa-Ankerhold
1,3,†,
Manuel Lasch
1,2,4,† and
Elisabeth Deindl
1,2,*,†
1
Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
2
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany
3
Department of Internal Medicine I, Faculty of Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
4
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(11), 5800; https://doi.org/10.3390/ijms22115800
Submission received: 15 April 2021 / Revised: 26 May 2021 / Accepted: 27 May 2021 / Published: 28 May 2021

Abstract

The complement system is a potent inflammatory trigger, activator, and chemoattractant for leukocytes, which play a crucial role in promoting angiogenesis. However, little information is available about the influence of the complement system on angiogenesis in ischemic muscle tissue. To address this topic and analyze the impact of the complement system on angiogenesis, we induced muscle ischemia in complement factor C3 deficient (C3−/−) and wildtype control mice by femoral artery ligation (FAL). At 24 h and 7 days after FAL, we isolated the ischemic gastrocnemius muscles and investigated them by means of (immuno-)histological analyses. C3−/− mice showed elevated ischemic damage 7 days after FAL, as evidenced by H&E staining. In addition, angiogenesis was increased in C3−/− mice, as demonstrated by increased capillary/muscle fiber ratio and increased proliferating endothelial cells (CD31+/BrdU+). Moreover, our results showed that the total number of leukocytes (CD45+) was increased in C3−/− mice, which was based on an increased number of neutrophils (MPO+), neutrophil extracellular trap formation (MPO+/CitH3+), and macrophages (CD68+) displaying a shift toward an anti-inflammatory and pro-angiogenic M2-like polarized phenotype (CD68+/MRC1+). In summary, we show that the deficiency of complement factor C3 increased neutrophil and M2-like polarized macrophage accumulation in ischemic muscle tissue, contributing to angiogenesis.
Keywords: angiogenesis; complement system; C3; leukocytes; macrophages; macrophage polarization; neutrophils; neutrophil extracellular traps; NETs; ischemia angiogenesis; complement system; C3; leukocytes; macrophages; macrophage polarization; neutrophils; neutrophil extracellular traps; NETs; ischemia

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MDPI and ACS Style

Götz, P.; Braumandl, A.; Kübler, M.; Kumaraswami, K.; Ishikawa-Ankerhold, H.; Lasch, M.; Deindl, E. C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue. Int. J. Mol. Sci. 2021, 22, 5800. https://doi.org/10.3390/ijms22115800

AMA Style

Götz P, Braumandl A, Kübler M, Kumaraswami K, Ishikawa-Ankerhold H, Lasch M, Deindl E. C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue. International Journal of Molecular Sciences. 2021; 22(11):5800. https://doi.org/10.3390/ijms22115800

Chicago/Turabian Style

Götz, Philipp, Anna Braumandl, Matthias Kübler, Konda Kumaraswami, Hellen Ishikawa-Ankerhold, Manuel Lasch, and Elisabeth Deindl. 2021. "C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue" International Journal of Molecular Sciences 22, no. 11: 5800. https://doi.org/10.3390/ijms22115800

APA Style

Götz, P., Braumandl, A., Kübler, M., Kumaraswami, K., Ishikawa-Ankerhold, H., Lasch, M., & Deindl, E. (2021). C3 Deficiency Leads to Increased Angiogenesis and Elevated Pro-Angiogenic Leukocyte Recruitment in Ischemic Muscle Tissue. International Journal of Molecular Sciences, 22(11), 5800. https://doi.org/10.3390/ijms22115800

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