Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

TAFI deficiency causes maladaptive vascular remodeling after hemophilic joint bleeding

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Prehospital plasma is associated with distinct biomarker expression following injury

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The R213G polymorphism in SOD3 protects against allergic airway inflammation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The collagen receptor uPARAP/Endo180 regulates collectins through unique structural elements in its FNII domain

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cellular uptake of collagens and implications for immune cell regulation in disease

    Research output: Contribution to journalReviewResearchpeer-review

  4. CCL2/MCP-1 signaling drives extracellular matrix turnover by diverse macrophage subsets

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Tine Wyseure
  • Tingyi Yang
  • Jenny Y Zhou
  • Esther J Cooke
  • Bettina Wanko
  • Merissa Olmer
  • Ruchi Agashe
  • Yosuke Morodomi
  • Niels Behrendt
  • Martin Lotz
  • John Morser
  • Annette von Drygalski
  • Laurent O Mosnier
View graph of relations

Excessive vascular remodeling is characteristic of hemophilic arthropathy (HA) and may contribute to joint bleeding and the progression of HA. Mechanisms for pathological vascular remodeling after hemophilic joint bleeding are unknown. In hemophilia, activation of thrombin-activatable fibrinolysis inhibitor (TAFI) is impaired, which contributes to joint bleeding and may also underlie the aberrant vascular remodeling. Here, hemophilia A (factor VIII–deficient; FVIII-deficient) mice or TAFI-deficient mice with transient (antibody-induced) hemophilia A were used to determine the role of FVIII and TAFI in vascular remodeling after joint bleeding. Excessive vascular remodeling and vessel enlargement persisted in FVIII-deficient and TAFI-deficient mice, but not in transient hemophilia WT mice, after similar joint bleeding. TAFI-overexpression in FVIII-deficient mice prevented abnormal vessel enlargement and vascular leakage. Age-related vascular changes were observed with FVIII or TAFI deficiency and correlated positively with bleeding severity after injury, supporting increased vascularity as a major contributor to joint bleeding. Antibody-mediated inhibition of uPA also prevented abnormal vascular remodeling, suggesting that TAFI’s protective effects include inhibition of uPA-mediated plasminogen activation. In conclusion, the functional TAFI deficiency in hemophilia drives maladaptive vascular remodeling in the joints after bleeding. These mechanistic insights allow targeted development of potentially new strategies to normalize vascularity and control rebleeding in HA.

Original languageEnglish
Article numbere128379
JournalJCI Insight
Volume4
Issue number19
ISSN2379-3708
DOIs
Publication statusPublished - 3 Oct 2019

ID: 58014893