{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:22:48Z","timestamp":1791339768667,"version":"4.3.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Gene therapy for severe von Willebrand disease (vWD) seems an interesting treatment alternative with long-term therapeutic potential. We investigated the feasibility of targeting the liver for ectopic expression of physiologically active von Willebrand factor (vWF).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            The capacity of transgene-encoded murine vWF to restore vWF function was studied in a mouse model of severe vWD after liver-specific gene transfer by hydrodynamic injection. By using a hepatocyte-specific \u03b11 antitrypsin promoter, a considerably higher and longer-lasting vWF expression was obtained when compared with a cytomegalovirus promoter, reaching maximum vWF plasma levels that are 10\u00b11 times higher than the wild-type level. Liver-expressed vWF showed the full range of multimers, including the high molecular weight multimers, and restored factor VIII plasma levels, consistent with correction of the bleeding time 3 but not 7 days after gene transfer. Importantly, transgene encoded plasma vWF restored proper platelet adhesion and aggregation in a FeCl\n            <jats:sub>3<\/jats:sub>\n            induced thrombosis model.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            High ectopic expression of transgene encoded plasma vWF can be obtained after gene transfer to the liver. Liver-expressed vWF was fully multimerized and able to restore proper platelet plug formation in severe vWD. The liver therefore seems an attractive target for gene therapy for severe vWD.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.108.168369","type":"journal-article","created":{"date-parts":[[2008,6,13]],"date-time":"2008-06-13T02:18:25Z","timestamp":1213323505000},"page":"1621-1626","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":65,"title":["Restoration of Plasma von Willebrand Factor Deficiency Is Sufficient to Correct Thrombus Formation After Gene Therapy for Severe von Willebrand Disease"],"prefix":"10.1161","volume":"28","author":[{"given":"Simon F.","family":"De Meyer","sequence":"first","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nele","family":"Vandeputte","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Pareyn","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Petrus","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Lenting","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinee K.L.","family":"Chuah","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"VandenDriessche","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Deckmyn","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vanhoorelbeke","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research (S.F.D.M., N.V., I. Pareyn, H.D., K.V.), K.U. Leuven Campus Kortrijk, Belgium; the Center for Transgene Technology and Gene Therapy (I. Petrus, M.K.L.C., T.V.), Flanders Institute for Biotechnology (VIB), University of Leuven, Belgium; and the Laboratory for Thrombosis and Haemostasis (P.J.L.), Department of Clinical Chemistry &amp; Haematology, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200303000-00008"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613992"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2005.12.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-054718"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2330"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3605"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1992.3.6-641"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.8.4406"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2000.0075"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0333"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9524"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300947"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950017734"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199806000-00009"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.5.1637"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3555"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01218-4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.18.10379"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3217"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.3.813"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/4751"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0823"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7701119"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.178"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.10.2644.2644"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2455"},{"key":"e_1_3_3_27_2","first-page":"620","volume":"26","year":"1998","unstructured":"Andre P, Brouland JP, Roussi J, Bonneau M, Pignaud G, Bal dit SC, Hainaud P, Vaiman M, Drouet L. 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