{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:09:17Z","timestamp":1791274157316,"version":"4.1.0"},"reference-count":35,"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":[[2001,4,27]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Cell proliferation and cell death (either necrosis or apoptosis) are key processes in the progression of atherosclerosis. The tumor suppressor gene p53 is an essential gene in cell proliferation and cell death and is upregulated in human atherosclerotic plaques, both in smooth muscle cells and in macrophages. In the present study, we investigated the importance of macrophage p53 in the progression of atherosclerosis using bone marrow transplantation in APOE*3-Leiden transgenic mice, an animal model for human-like atherosclerosis. APOE*3-Leiden mice were lethally irradiated and reconstituted with bone marrow derived from either p53-deficient (\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) or control (\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            ) donor mice. Reconstitution of mice with\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            bone marrow did not result in any hemopoietic abnormalities as compared with\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            transplanted mice. After 12 weeks on an atherogenic diet, APOE*3-Leiden mice reconstituted with\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            bone marrow showed a significant (\n            <jats:italic>P<\/jats:italic>\n            =0.006) 2.3-fold increase in total atherosclerotic lesion area as compared with mice reconstituted with\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            bone marrow. Although likely a secondary effect of the increased lesion area,\n            <jats:italic>p53<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            transplanted mice also showed significantly more lesion necrosis (necrotic index, 1.1\u00b11.3 versus 0.2\u00b10.7;\n            <jats:italic>P<\/jats:italic>\n            =0.04) and lesion macrophages (macrophage area, 79.9\u00b140.0 versus 39.7\u00b127.3\u00d710\n            <jats:sup>3<\/jats:sup>\n            \u03bcm\n            <jats:sup>2<\/jats:sup>\n            per section;\n            <jats:italic>P<\/jats:italic>\n            =0.02). These observations coincided with a tendency toward decreased apoptosis (terminal deoxynucleotidyl transferase end-labeling [TUNEL]\u2013positive nuclei going from 0.42\u00b10.39 to 0.14\u00b10.15%,\n            <jats:italic>P<\/jats:italic>\n            =0.071), whereas the number of proliferating cells (5\u2032-bromo-2\u2032-deoxyuridine\u2013positive nuclei) was not affected (3.75\u00b10.98 versus 4.77\u00b12.30%;\n            <jats:italic>P<\/jats:italic>\n            =0.59). These studies indicate that macrophage p53 is important in suppressing the progression of atherosclerosis and identify a novel therapeutic target for regulating plaque stability.\n          <\/jats:p>","DOI":"10.1161\/hh0801.089261","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:32:49Z","timestamp":1191004369000},"page":"780-786","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":122,"title":["Macrophage p53 Deficiency Leads to Enhanced Atherosclerosis in APOE*3-Leiden Transgenic Mice"],"prefix":"10.1161","volume":"88","author":[{"given":"Bart J.M.","family":"van Vlijmen","sequence":"first","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gery","family":"Gerritsen","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur L.","family":"Franken","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianne S.M.","family":"Boesten","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Kockx","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion J.","family":"Gijbels","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel P.","family":"Vierboom","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"van Eck","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"van de Water","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo J.C.","family":"van Berkel","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Havekes","sequence":"additional","affiliation":[{"name":"From the Departments of Biopharmaceutics (B.J.M.v.V., G.G., L.S.M.B., M.v.E., T.J.C.v.B.) and Toxicology (A.L.F., B.v.d.W.), Leiden\/Amsterdam Center for Drug Research, Leiden\/Amsterdam Center for Drug Research, Leiden, the Netherlands; TNO Prevention and Health (B.J.M.v.V., G.G., A.L.F., L.S.M.B., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; Department of Pathology AZ-Middelheim (M.M.K.), University of Antwerp, Antwerp, Belgium; and Departments of Human Genetics (M.J.G.), Immunohematology..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"269","volume":"26","year":"1996","unstructured":"Fuster V, Badimon J, Chesebro JH, Fallon JT. 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