{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:54:47Z","timestamp":1790848487481,"version":"4.1.0"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Tissue-resident macrophages (T-RM\u00f8s) accumulate at sites predisposed to atherosclerosis in the healthy aortic intima. T-RM\u00f8s require local cues for their maintenance, but the niche signals governing their persistence in arterial tissue remain poorly defined. Here, we identify distinct, spatially compartmentalized sources of CSF1 (colony-stimulating factor 1) that regulate T-RM\u00f8 populations in the healthy aorta and during atherosclerosis, a chronic inflammatory disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Conditional\n                      <jats:italic toggle=\"yes\">Csf1<\/jats:italic>\n                      gene deletion (global, endothelial, arterial endothelial, and mesenchymal cell) or systemic antibody blockade was performed in normal or hypercholesterolemic\n                      <jats:italic toggle=\"yes\">Ldlr<\/jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice.\n                      <jats:italic toggle=\"yes\">Cx3cr1<\/jats:italic>\n                      lineage tracing of T-RM\u00f8s initiated before hypercholesterolemia distinguished these cells from monocyte-derived macrophages in atherosclerotic lesions. Bone marrow transplantation enabled lineage tracing of T-RM\u00f8s and\n                      <jats:italic toggle=\"yes\">Csf1<\/jats:italic>\n                      deletion in endothelial cells.\n                      <jats:italic toggle=\"yes\">Ccr2<\/jats:italic>\n                      lineage tracing directly assessed monocyte-derived macrophages. A novel en face immunoconfocal microscopy approach accurately enumerated macrophages in aortic lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Conditional\n                      <jats:italic toggle=\"yes\">Csf1<\/jats:italic>\n                      deletion revealed that arterial endothelial cell-derived CSF1 is essential for T-RM\u00f8 steady-state maintenance. In contrast, adventitial macrophages rely on CSF1 produced by PDGFR\u03b2-expressing mesenchymal, but not endothelial, cells. CSF1 primarily supports intimal macrophage proliferation and retention rather than survival. Postnatal parabiosis revealed only occasional clusters of parabiont blood monocyte-derived macrophages in the normal intima. During hypercholesterolemia-initiated atherogenesis, the abundance of T-RM\u00f8s increases then gradually declines, while an inflammatory response consisting of monocyte recruitment progressively expands the total number of lesion macrophages. Endothelial, but not mesenchymal, CSF1 is required for optimal macrophage accumulation in 4-week foam cell lesions. Lineage tracing showed that CSF1, specifically endothelial-derived CSF1, is required for the maintenance of T-RM\u00f8s, but not monocyte-derived macrophages, in atherosclerotic lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our study uncovers a unique role of local endothelial cell CSF1 in maintaining the intimal, but not adventitial, T-RM\u00f8 niche during homeostasis and early stages of atherosclerosis and reveals that maintenance of monocyte-derived macrophages in lesions is distinct.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.126.328541","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:00:25Z","timestamp":1790845225000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Arterial Resident But Not 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M.I.C.)."},{"name":"Department of Laboratory Medicine and Pathobiology (M.G.A., H.M.I., S.P., M.R., C.K.P., C.S.R., M.I.C.), University of Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-0300","authenticated-orcid":true,"given":"Sharon J.","family":"Hyduk","sequence":"additional","affiliation":[{"name":"University Health Network Research Institutes, Peter Munk Cardiac Centre, Toronto, ON, Canada (M.G.A., H.M.I., S.J.H., S.P., M.R., E.A.-C., C.A.S., C.K.P., S.A.D., S.E., C.S.R., M.I.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4085-3539","authenticated-orcid":true,"given":"Stylianos","family":"Prattas","sequence":"additional","affiliation":[{"name":"University Health Network Research Institutes, Peter Munk Cardiac Centre, Toronto, ON, Canada (M.G.A., H.M.I., S.J.H., S.P., M.R., E.A.-C., C.A.S., C.K.P., S.A.D., S.E., C.S.R., M.I.C.)."},{"name":"Department of 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