{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:18:12Z","timestamp":1791289092850,"version":"4.3.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,5]]},"abstract":"\n Objective\u2014<\/jats:title>\n \n Coronary heart disease is associated with monocytosis. Studies using animal models of monocytosis and atherosclerosis such as\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice have shown bone marrow (BM) hematopoietic stem and multipotential progenitor cell (HSPC) expansion, associated with increased cell surface expression of the common \u03b2 subunit of the granulocyte macrophage colony\u2013stimulating factor\/interleukin-3 receptor (CBS) on HSPCs.\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice also display increased granulocyte macrophage colony\u2013stimulating factor\u2013dependent monocyte production in the spleen. We investigated the role of the CBS in cholesterol-driven HSPC expansion, monocytosis, and atherosclerosis.\n <\/jats:p>\n <\/jats:sec>\n \n Approach and Results\u2014<\/jats:title>\n \n Ldlr<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice were transplanted with\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n Cbs<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n or\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM followed by Western-type diet feeding. Compared with\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM\u2013transplanted controls,\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n Cbs<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM\u2013transplanted mice had reduced BM and splenic HSPC proliferation, fewer blood monocytes and neutrophils, and reduced macrophage content and area of early atherosclerotic lesions. More advanced lesions showed diminished macrophage and collagen content; however, lesion size was unchanged, reflecting an increase in necrotic core area, associated with a marked decrease in\n Abcg1<\/jats:italic>\n expression and increased macrophage apoptosis. Compared with wild-type mice, Western-type diet\u2013fed\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice showed increased CBS expression on granulocyte macrophage colony\u2013stimulating factor\u2013producing innate response activator B cells and expansion of this population.\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n Cbs<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM\u2013transplanted\n Ldlr<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice showed a marked decrease in innate response activator B cells compared with\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM\u2013transplanted\n Ldlr<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n controls.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions\u2014<\/jats:title>\n \n Increased levels of CBS on HSPCs and splenic innate response activator B cells lead to expansion of these populations in\n ApoE<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n BM\u2013transplanted\n Ldlr<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice, contributing to monocytosis and increased lesional macrophage content. However, in more advanced lesions, the CBS also has a role in atherosclerotic plaque stabilization.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.113.303097","type":"journal-article","created":{"date-parts":[[2014,3,21]],"date-time":"2014-03-21T05:29:57Z","timestamp":1395379797000},"page":"976-984","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Interleukin-3\/Granulocyte Macrophage Colony\u2013Stimulating Factor Receptor Promotes Stem Cell Expansion, Monocytosis, and Atheroma Macrophage Burden in Mice With Hematopoietic\n ApoE<\/i>\n Deficiency"],"prefix":"10.1161","volume":"34","author":[{"given":"Mi","family":"Wang","sequence":"first","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikandan","family":"Subramanian","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Abramowicz","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayelet","family":"Gonen","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Witztum","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Welch","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Tabas","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Westerterp","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. Wang), Columbia University, New York, NY; Department of Medicine, University of California San Diego, La Jolla (A.G., J.W.); and Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M. Westerterp)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Tall","sequence":"additional","affiliation":[{"name":"From the Division of Molecular Medicine, Department of Medicine (M. Wang, M.S., S.A., A.J.M., C.W., I.T., M. Westerterp, A.R.T.) and Department of Pharmacology (M. 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