Cobra Venom Factor Boosts Arteriogenesis in Mice
Arteriogenesis, the growth of natural bypass blood vessels, can compensate for the loss of arteries caused by vascular occlusive diseases. Accordingly, it is a major goal to identify the drugs promoting this innate immune system-driven process in patients aiming to save their tissues and life. Here,...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8454 |
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| author | Philipp Götz Sharon O. Azubuike-Osu Anna Braumandl Christoph Arnholdt Matthias Kübler Lisa Richter Manuel Lasch Lisa Bobrowski Klaus T. Preissner Elisabeth Deindl |
| author_facet | Philipp Götz Sharon O. Azubuike-Osu Anna Braumandl Christoph Arnholdt Matthias Kübler Lisa Richter Manuel Lasch Lisa Bobrowski Klaus T. Preissner Elisabeth Deindl |
| author_sort | Philipp Götz |
| collection | DOAJ |
| description | Arteriogenesis, the growth of natural bypass blood vessels, can compensate for the loss of arteries caused by vascular occlusive diseases. Accordingly, it is a major goal to identify the drugs promoting this innate immune system-driven process in patients aiming to save their tissues and life. Here, we studied the impact of the Cobra venom factor (CVF), which is a C3-like complement-activating protein that induces depletion of the complement in the circulation in a murine hind limb model of arteriogenesis. Arteriogenesis was induced in C57BL/6J mice by femoral artery ligation (FAL). The administration of a single dose of CVF (12.5 µg) 24 h prior to FAL significantly enhanced the perfusion recovery 7 days after FAL, as shown by Laser Doppler imaging. Immunofluorescence analyses demonstrated an elevated number of proliferating (BrdU<sup>+</sup>) vascular cells, along with an increased luminal diameter of the grown collateral vessels. Flow cytometric analyses of the blood samples isolated 3 h after FAL revealed an elevated number of neutrophils and platelet-neutrophil aggregates. Giemsa stains displayed augmented mast cell recruitment and activation in the perivascular space of the growing collaterals 8 h after FAL. Seven days after FAL, we found more CD68<sup>+</sup>/MRC-1<sup>+</sup> M2-like polarized pro-arteriogenic macrophages around growing collaterals. These data indicate that a single dose of CVF boosts arteriogenesis by catalyzing the innate immune reactions, relevant for collateral vessel growth. |
| first_indexed | 2024-03-09T05:21:26Z |
| format | Article |
| id | doaj.art-a1ccb0b02bd94f17b820a1355f72165d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:21:26Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a1ccb0b02bd94f17b820a1355f72165d2023-12-03T12:40:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315845410.3390/ijms23158454Cobra Venom Factor Boosts Arteriogenesis in MicePhilipp Götz0Sharon O. Azubuike-Osu1Anna Braumandl2Christoph Arnholdt3Matthias Kübler4Lisa Richter5Manuel Lasch6Lisa Bobrowski7Klaus T. Preissner8Elisabeth Deindl9Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyFlow Cytometry Core Facility, Biomedical Center, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyDepartment of Cardiology, Kerckhoff-Heart Research Institute, Faculty of Medicine, Justus Liebig University, 35392 Giessen, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyArteriogenesis, the growth of natural bypass blood vessels, can compensate for the loss of arteries caused by vascular occlusive diseases. Accordingly, it is a major goal to identify the drugs promoting this innate immune system-driven process in patients aiming to save their tissues and life. Here, we studied the impact of the Cobra venom factor (CVF), which is a C3-like complement-activating protein that induces depletion of the complement in the circulation in a murine hind limb model of arteriogenesis. Arteriogenesis was induced in C57BL/6J mice by femoral artery ligation (FAL). The administration of a single dose of CVF (12.5 µg) 24 h prior to FAL significantly enhanced the perfusion recovery 7 days after FAL, as shown by Laser Doppler imaging. Immunofluorescence analyses demonstrated an elevated number of proliferating (BrdU<sup>+</sup>) vascular cells, along with an increased luminal diameter of the grown collateral vessels. Flow cytometric analyses of the blood samples isolated 3 h after FAL revealed an elevated number of neutrophils and platelet-neutrophil aggregates. Giemsa stains displayed augmented mast cell recruitment and activation in the perivascular space of the growing collaterals 8 h after FAL. Seven days after FAL, we found more CD68<sup>+</sup>/MRC-1<sup>+</sup> M2-like polarized pro-arteriogenic macrophages around growing collaterals. These data indicate that a single dose of CVF boosts arteriogenesis by catalyzing the innate immune reactions, relevant for collateral vessel growth.https://www.mdpi.com/1422-0067/23/15/8454arteriogenesiscomplement systemC3cobra venom factormast cellsmacrophages |
| spellingShingle | Philipp Götz Sharon O. Azubuike-Osu Anna Braumandl Christoph Arnholdt Matthias Kübler Lisa Richter Manuel Lasch Lisa Bobrowski Klaus T. Preissner Elisabeth Deindl Cobra Venom Factor Boosts Arteriogenesis in Mice International Journal of Molecular Sciences arteriogenesis complement system C3 cobra venom factor mast cells macrophages |
| title | Cobra Venom Factor Boosts Arteriogenesis in Mice |
| title_full | Cobra Venom Factor Boosts Arteriogenesis in Mice |
| title_fullStr | Cobra Venom Factor Boosts Arteriogenesis in Mice |
| title_full_unstemmed | Cobra Venom Factor Boosts Arteriogenesis in Mice |
| title_short | Cobra Venom Factor Boosts Arteriogenesis in Mice |
| title_sort | cobra venom factor boosts arteriogenesis in mice |
| topic | arteriogenesis complement system C3 cobra venom factor mast cells macrophages |
| url | https://www.mdpi.com/1422-0067/23/15/8454 |
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