{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:57:09Z","timestamp":1791943029282,"version":"4.3.4"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      Expression of the extrahepatic acute-phase protein Saa3 (serum amyloid A3) increases in response to acute and chronic inflammatory stimuli and is elevated in adipose tissue and macrophages in obese mice. A recent report suggested that Saa3 is proatherogenic in male\n                      <jats:italic>ApoE<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Because of our previous observation that female but not male Saa3-deficient mice are protected from obesity, adipose inflammation, and hyperlipidemia, we sought to determine whether Saa3 differentially modulates atherosclerosis in mice of both sexes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      To promote atherosclerosis,\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      and\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      male and female mice were crossed with\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. All mice consumed a diet high in saturated fat and sucrose with 0.15% added cholesterol for 16 weeks. Plasma lipids and atherosclerosis levels were assessed. Female\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited elevated cholesterol levels relative to\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      controls and exhibited increased atherosclerosis, while male\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were protected from atherosclerosis. Data from the hybrid mouse diversity panel revealed that Saa3 associates strongly with inflammatory, Trem2-associated, and tissue remodeling genes and pathways in males but not females, an effect confirmed in liver tissue, atherosclerotic lesions, and cultured macrophages. Macrophages isolated from male and female mice showed differential inflammatory effects of Saa3 deficiency, an effect linked with sex steroid signaling. Cholesterol efflux capacity was increased in\n                      <jats:italic>Saa3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      males only.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Saa3 is proatherogenic in male but atheroprotective in female mice, effects that may be related to sex-specific relationships between Saa3, cholesterol metabolism, inflammatory genes, and Trem2 macrophages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.121.316066","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T05:01:51Z","timestamp":1616648511000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Sexually Dimorphic Relationships Among Saa3 (Serum Amyloid A3), Inflammation, and Cholesterol Metabolism Modulate Atherosclerosis in Mice"],"prefix":"10.1161","volume":"41","author":[{"given":"Alan","family":"Chait","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle."},{"name":"Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle."},{"name":"Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, 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