Ex Vivo Modeling of the PC (Protein C) Pathway Using Endothelial Cells and Plasma: A Personalized Approach Article Swipe
Nadine Schwarz
,
Jens Müller
,
Hamideh Yadegari
,
Hannah L. McRae
,
Sara Reda
,
Nasim Shahidi Hamedani
,
Johannes Oldenburg
,
Bernd Pötzsch
,
Heiko Rühl
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1161/atvbaha.122.318433
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1161/atvbaha.122.318433
Background: The endothelial cell–dependent PC (protein C) pathway is critically involved in the regulation of coagulation, anti-inflammatory, and cytoprotective signaling. Its reactivity shows high interindividual variability, and it contributes to prothrombotic disorders, such as the FVL (factor V Leiden) mutation. Methods: Endothelial colony–forming cells (ECFCs) were isolated from heparinized peripheral blood from healthy individuals and FVL carriers. Confluent monolayers of ECFCs were overlaid with plasma, and thrombin formation was initiated by addition of tissue factor (1 pmol/L). Subsequently, thrombin and APC (activated PC) formation rates were measured over time using oligonucleotide-based enzyme capture assays. To induce downregulation of TM (thrombomodulin) expression, ECFCs were stimulated with IL-1β (interleukin 1β). In vivo APC response rates were monitored in study participants after infusion of low-dose rFVIIa (recombinant activated factor VII). Results: The median peak APC concentration was 1.12 nmol/L in experiments with IL-1β stimulated ECFCs and 3.66 nmol/L without IL-1β. Although thrombin formation rates were comparable, APC formation rates were significantly higher in FVL carriers (n=6) compared to noncarriers (n=5) as evidenced by a higher ratio between the area under the curve of APC generation to the area under the curve of thrombin generation (median 0.090 versus 0.031, P =0.017). These ex vivo results were correlated with an increased APC response to rFVIIa-induced thrombin formation in FVL carriers in vivo. Conclusions: Patient-specific ex vivo modeling of the PC pathway was achieved using blood-derived ECFCs. The correlation between in and ex vivo APC response rates confirms that the autologous PC model accurately depicts the in vivo situation.
Related Topics
Concepts
Ex vivo
Thrombomodulin
In vivo
Thrombin
Endothelial protein C receptor
Molecular biology
Protein C
Tissue factor
Chemistry
Immunology
Coagulation
Medicine
Biology
Internal medicine
Biochemistry
Platelet
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1161/atvbaha.122.318433
- https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.122.318433
- OA Status
- bronze
- Cited By
- 6
- References
- 30
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4308680136
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4308680136Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1161/atvbaha.122.318433Digital Object Identifier
- Title
-
Ex Vivo Modeling of the PC (Protein C) Pathway Using Endothelial Cells and Plasma: A Personalized ApproachWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-11-10Full publication date if available
- Authors
-
Nadine Schwarz, Jens Müller, Hamideh Yadegari, Hannah L. McRae, Sara Reda, Nasim Shahidi Hamedani, Johannes Oldenburg, Bernd Pötzsch, Heiko RühlList of authors in order
- Landing page
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https://doi.org/10.1161/atvbaha.122.318433Publisher landing page
- PDF URL
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https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.122.318433Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.122.318433Direct OA link when available
- Concepts
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Ex vivo, Thrombomodulin, In vivo, Thrombin, Endothelial protein C receptor, Molecular biology, Protein C, Tissue factor, Chemistry, Immunology, Coagulation, Medicine, Biology, Internal medicine, Biochemistry, Platelet, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2023: 3Per-year citation counts (last 5 years)
- References (count)
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30Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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