Elevated soluble Flt1 inhibits endothelial repair in PR3-ANCA-associated vasculitis
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti-proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-associated vasculitis, leading to an antiangiogenic state that hinders endothelial repair.
| Errataetall: |
CommentIn: J Am Soc Nephrol. 2012 Jan;23(1):8-10. - PMID 22173697 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 23(2012), 1 vom: 21. Jan., Seite 155-64 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Le Roux, Sandrine [VerfasserIn] |
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| Links: |
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| Themen: |
80295-54-1 |
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| Anmerkungen: |
Date Completed 09.03.2012 Date Revised 29.01.2022 published: Print-Electronic CommentIn: J Am Soc Nephrol. 2012 Jan;23(1):8-10. - PMID 22173697 Citation Status MEDLINE |
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| doi: |
10.1681/ASN.2010080858 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM212570811 |
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| 245 | 1 | 0 | |a Elevated soluble Flt1 inhibits endothelial repair in PR3-ANCA-associated vasculitis |
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| 500 | |a CommentIn: J Am Soc Nephrol. 2012 Jan;23(1):8-10. - PMID 22173697 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti-proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-associated vasculitis, leading to an antiangiogenic state that hinders endothelial repair | ||
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| 700 | 1 | |a Dufay, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Néel, Mélanie |e verfasserin |4 aut | |
| 700 | 1 | |a Meffray, Emmanuelle |e verfasserin |4 aut | |
| 700 | 1 | |a Lamandé, Noël |e verfasserin |4 aut | |
| 700 | 1 | |a Rimbert, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Josien, Régis |e verfasserin |4 aut | |
| 700 | 1 | |a Hamidou, Mohamed |e verfasserin |4 aut | |
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| 700 | 1 | |a Salama, Alan D |e verfasserin |4 aut | |
| 700 | 1 | |a Fakhouri, Fadi |e verfasserin |4 aut | |
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