{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:43:59Z","timestamp":1792539839833,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,9,29]]},"abstract":"<jats:sec><jats:title><jats:underline>Rationale:<\/jats:underline><\/jats:title><jats:p>Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Objective:<\/jats:underline><\/jats:title><jats:p>We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Methods and Results:<\/jats:underline><\/jats:title><jats:p>In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava. We demonstrated that 2 strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. MCs were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the inferior vena cava wall after DVT induction were reduced in MC-deficient mice. Stenosis application increased plasma levels of soluble P-selectin in wild-type but not in MC-deficient mice. MC releasate elevated ICAM-1 (intercellular adhesion molecule-1) expression on HUVEC (human umbilical vein endothelial cells) in vitro. Topical application of compound 48\/80, an MC secretagogue, or histamine, a Weibel\u2013Palade body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine restored thrombosis in MC-deficient animals.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Conclusions:<\/jats:underline><\/jats:title><jats:p>MCs exacerbate DVT likely through endothelial activation and Weibel\u2013Palade body release, which is, at least in part, mediated by histamine. Because MCs do not directly contribute to normal hemostasis, they can be considered potential targets for prevention of DVT in humans.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circresaha.117.311185","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:55:19Z","timestamp":1500944119000},"page":"941-950","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice"],"prefix":"10.1161","volume":"121","author":[{"given":"Tatyana","family":"Ponomaryov","sequence":"first","affiliation":[{"name":"From the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom (T.P., H.P., L.F., A.B.); Department of Cardiology, University Hospital Birmingham, United Kingdom (L.F.); Program in Cellular and Molecular Medicine (D.D.W., A.B.) and Division of Hematology\/Oncology (D.D.W., A.B.), Boston Children\u2019s Hospital, MA; and Department of Pediatrics, Harvard Medical School, Boston, MA (D.D.W., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Payne","sequence":"additional","affiliation":[{"name":"From the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom (T.P., H.P., L.F., A.B.); Department of Cardiology, University Hospital Birmingham, United Kingdom (L.F.); Program in Cellular and Molecular Medicine (D.D.W., A.B.) and Division of Hematology\/Oncology (D.D.W., A.B.), Boston Children\u2019s Hospital, MA; and Department of Pediatrics, Harvard Medical School, Boston, MA (D.D.W., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Fabritz","sequence":"additional","affiliation":[{"name":"From the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom (T.P., H.P., L.F., A.B.); Department of Cardiology, University Hospital Birmingham, United Kingdom (L.F.); Program in Cellular and Molecular Medicine (D.D.W., A.B.) and Division of Hematology\/Oncology (D.D.W., A.B.), Boston Children\u2019s Hospital, MA; and Department of Pediatrics, Harvard Medical School, Boston, MA (D.D.W., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa D.","family":"Wagner","sequence":"additional","affiliation":[{"name":"From the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom (T.P., H.P., L.F., A.B.); Department of Cardiology, University Hospital Birmingham, United Kingdom (L.F.); Program in Cellular and Molecular Medicine (D.D.W., A.B.) and Division of Hematology\/Oncology (D.D.W., A.B.), Boston Children\u2019s Hospital, MA; and Department of Pediatrics, Harvard Medical School, Boston, MA (D.D.W., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Brill","sequence":"additional","affiliation":[{"name":"From the Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom (T.P., H.P., L.F., A.B.); Department of Cardiology, University Hospital Birmingham, United Kingdom (L.F.); Program in Cellular and Molecular Medicine (D.D.W., A.B.) and Division of Hematology\/Oncology (D.D.W., A.B.), Boston Children\u2019s Hospital, MA; and Department of Pediatrics, Harvard Medical School, Boston, MA (D.D.W., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-015-1311-6"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.6.585"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00024-2016"},{"key":"e_1_3_5_5_2","volume-title":"The Surgeon General\u2019s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism","author":"Office of the Surgeon General (US)","year":"2008","unstructured":"Office of the Surgeon General (US). 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