{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:21:37Z","timestamp":1792095697135,"version":"4.4.0"},"reference-count":103,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-laden foam cells and plaques within the arterial wall. Dysfunctional vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells, and macrophages contribute to disease progression. Here, we report that macrophage-specific expression of epsins, highly conserved endocytic adaptor proteins involved in clathrin-mediated endocytosis, accelerates atherosclerosis in Western diet\u2013fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      WT\/Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (wild-type\/Apoe-deficient) mice and littermates with a LysM-DKO\/Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (myeloid-specific deletion of epsin 1\/2 on an Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      background) were generated and fed a Western diet for 16 weeks. Single-cell RNA sequencing was conducted to investigate the cellular and molecular mechanisms regulated by macrophage epsins during atherosclerosis. Findings from single-cell RNA sequencing were validated through metabolic profiling, qRT-PCR (quantitative reverse transcription polymerase chain reaction), immunostaining, and coculture experiments to assess associated phenotypic changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      LysM-DKO\/Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited significantly reduced atherosclerotic foam cell formation compared with WT\/Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      controls. Single-cell RNA sequencing analysis identified 19 major cell types, including 6 VSMC and 5 macrophage subpopulations. Modulated VSMC1 and VSMC2 subtypes were associated with inflammation, migration, and VSMC-to-macrophage transition. These populations, along with foamy-Trem2 and inflammatory macrophages, were markedly reduced in LysM-DKO\/Apoe\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Transition of modulated VSMC2 subtype into macrophages was significantly inhibited, as confirmed by both computational analysis and experimental validation. In addition, macrophage epsin deletion reversed endothelial dysfunction, suppressed cholesterol- and glucose-mediated signaling, and reduced expression of proinflammatory ligands IL (interleukin)-1\u03b2 and TNF-\u03b1 (tumor necrosis factor \u03b1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Macrophage epsin deletion limits foam cell formation and preserves VSMC and endothelial cell phenotypes and functions. These findings reveal a potential therapeutic strategy targeting macrophage epsins to combat atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.323288","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T09:00:12Z","timestamp":1757581212000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Single-Cell Analysis Reveals a Critical Role for Macrophage Epsins in Regulating the Origin of Foam Cells in Atherosclerosis"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3367-2669","authenticated-orcid":true,"given":"Kulandaisamy","family":"Arulsamy","sequence":"first","affiliation":[{"name":"Basic and Translational Research Division, Department of Cardiology, Boston Children\u2019s Hospital, MA (K.A., X.G., K.G., L.Z., K. Chen)."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA (K.A., X.G., K.G., L.Z., K. Chen)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-4932","authenticated-orcid":true,"given":"Kui","family":"Cui","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Harvard Medical School, MA (K. Cui, B.Z., B.W., S.E.-B., A.V., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-1094","authenticated-orcid":true,"given":"Bo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Harvard Medical School, MA (K. Cui, B.Z., B.W., S.E.-B., A.V., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8359-2518","authenticated-orcid":true,"given":"Beibei","family":"Wang","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Harvard Medical School, MA (K. Cui, B.Z., B.W., S.E.-B., A.V., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Eisa-Beygi","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Harvard Medical School, MA (K. Cui, B.Z., B.W., S.E.-B., A.V., H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Voronova","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Harvard Medical School, MA (K. 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