{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:01:55Z","timestamp":1791338515730,"version":"4.3.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The endothelial cell\u2013dependent 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Endothelial colony\u2013forming 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-1\u03b2 (interleukin 1\u03b2). In vivo APC response rates were monitored in study participants after infusion of low-dose rFVIIa (recombinant activated factor VII).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The median peak APC concentration was 1.12 nmol\/L in experiments with IL-1\u03b2 stimulated ECFCs and 3.66 nmol\/L without IL-1\u03b2. 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,\n              <jats:italic>P<\/jats:italic>\n              =0.017). These ex vivo results were correlated with an increased APC response to rFVIIa-induced thrombin formation in FVL carriers in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318433","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T10:00:17Z","timestamp":1668074417000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Ex Vivo Modeling of the PC (Protein C) Pathway Using Endothelial Cells and Plasma: A Personalized Approach"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-1515","authenticated-orcid":true,"given":"Nadine","family":"Schwarz","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamideh","family":"Yadegari","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah L.","family":"McRae","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Reda","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim Shahidi","family":"Hamedani","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"P\u00f6tzsch","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-2453","authenticated-orcid":true,"given":"Heiko","family":"R\u00fchl","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83649-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.6.1685"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31776-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500747200"},{"key":"e_1_3_3_6_2","first-page":"91","article-title":"Factor V and protein S as cofactors to activated protein C.","volume":"82","author":"Dahlb\u00e4ck B","year":"1997","unstructured":"Dahlb\u00e4ck, B. 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