ArticleBlood2022
Selective inhibition of activated protein C anticoagulant activity protects against hemophilic arthropathy in mice.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Challenges in Balancing Hemostasis and Thrombosis in Therapy Tailoring for Hemophilia: A Narrative Review.International journal of molecular sciences · 2026Review
- Dihydroartemisinin ameliorates hemarthrosis-induced cartilage degeneration by suppressing chondrocyte senescence via activation of Keap1-Nrf2 signaling pathway.Journal of orthopaedic translation · 2025Article
- Endothelial protein C receptor promotes retinal neovascularization through heme catabolism.Nature communications · 2025Article
- Divergent modulation of activated protein C pleiotropic functions by antibodies that differ by a single amino acid.Blood advances · 2025Article
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
- Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect.Bioactive materials · 2024Article
- A Novel Murine Model Enabling rAAV8-PC Gene Therapy for Severe Protein C Deficiency.International journal of molecular sciences · 2024Article
- Article
- Blood-Induced Arthropathy: A Major Disabling Complication of Haemophilia.Journal of clinical medicine · 2023Review
- Selective modulation of activated protein C activities by a nonactive site-targeting nanobody library.Blood advances · 2023Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Recurrent spontaneous or trauma-related bleeding into joints in hemophilia leads to hemophilic arthropathy (HA), a debilitating joint disease. Treatment of HA consists of preventing joint bleeding by clotting factor replacement, and in extreme cases, orthopedic surgery. We recently showed that administration of endothelial cell protein C receptor (EPCR) blocking monoclonal antibodies (mAb) markedly reduced the severity of HA in factor VIII (FVIII)-/- mice. EPCR blocking inhibits activated protein C (APC) generation and EPCR-dependent APC signaling. The present study was aimed to define the role of inhibition of APC anticoagulant activity, APC signaling, or both in suppressing HA. FVIII-/- mice were treated with a single dose of isotype control mAb, MPC1609 mAb, that inhibits anticoagulant, and signaling properties of APC, or MAPC1591 mAb that only blocks the anticoagulant activity of APC. Joint bleeding was induced by needle puncture injury. HA was evaluated by monitoring joint bleeding, change in joint diameter, and histopathological analysis of joint tissue sections for synovial hypertrophy, macrophage infiltration, neoangiogenesis, cartilage degeneration, and chondrocyte apoptosis. No significant differences were observed between MPC1609 and MAPC1591 in inhibiting APC anticoagulant activity in vitro and equally effective in correcting acute bleeding induced by the saphenous vein incision in FVIII-/- mice. Administration of MAPC1591, and not MPC1609, markedly reduced the severity of HA. MAPC1591 inhibited joint bleed-induced inflammatory cytokine interleukin-6 expression and vascular leakage in joints, whereas MPC1609 had no significant effect. Our data show that an mAb that selectively inhibits APC's anticoagulant activity without compromising its cytoprotective signaling offers a therapeutic potential alternative to treat HA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.