{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:16Z","timestamp":1792785856561,"version":"4.5.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL76246"],"award-info":[{"award-number":["R01 HL76246"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL85440"],"award-info":[{"award-number":["R01 HL85440"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL173191"],"award-info":[{"award-number":["R01 HL173191"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL174490"],"award-info":[{"award-number":["R01 HL174490"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PR181464"],"award-info":[{"award-number":["PR181464"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PR211352"],"award-info":[{"award-number":["PR211352"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["#24POST1191779"],"award-info":[{"award-number":["#24POST1191779"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Heart Association Career Development Awards","id":[{"id":"https:\/\/ror.org\/02xjhr934","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Infarct macrophages undergo dramatic phenotypic changes in response to cytokines and growth factors and serve as central effectors in cardiac repair and remodelling. Transforming growth factor (TGF)-\u03b2 superfamily members are key regulators of macrophages and signal predominantly through activation of Smad-dependent cascades. Although the involvement of TGF-\u03b2\/Smad3 in regulation of macrophage phenotype has been documented, the effects of Smad1 signalling on macrophage phenotype and function remain unknown. We aimed at examining the patterns of activation and role of macrophage Smad1 in repair and remodelling of the infarcted heart.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Macrophage Smad1 activation peaked 7 days after infarction. In vitro, TGF-\u03b21, TGF-\u03b23, and bone morphogenetic protein-6, potently stimulated Smad1 activation in bone marrow macrophages. To study the role of macrophage Smad1 in myocardial infarction, we generated mice with myeloid cell-specific Smad1 loss. Bioinformatic analysis of scRNA-seq data suggested broad activation of a Smad1-mediated transcriptional programme in all clusters of infarct macrophages. Myeloid cell-specific Smad1 loss attenuated post-infarction adverse remodelling and ventricular dysfunction, increasing angiogenesis and decreasing extracellular matrix denaturation. Proteomic and transcriptomic analysis suggested that acquisition of an angiogenic macrophage profile in the absence of Smad1 is associated with upregulation of the angiogenic mediators CXCL12 and osteopontin and attenuated expression of the angiostatic chemokine CXCL4. However, myeloid cell\u2013specific CXCL12 deletion in MyS1KO mice did not abolish the enhanced angiogenesis induced by Smad1 deficiency, indicating that Smad1-mediated suppression of angiogenesis likely depends on the coordinated regulation of multiple angiogenic pathways rather than on CXCL12 alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrate for the first time that macrophage Smad1 contributes to adverse post-infarction remodelling by regulating the balance between angiogenic and angiostatic signals and by enhancing extracellular matrix remodelling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag185","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:26:25Z","timestamp":1791282385000},"source":"Crossref","is-referenced-by-count":0,"title":["Macrophage Smad1 drives post-infarction dysfunction by reducing angiogenesis and by promoting matrix remodelling"],"prefix":"10.1093","author":[{"given":"Bijun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaibo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anis","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia C","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Tuleta","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["USA"]},{"name":"Departments of Neurology and Neuroscience, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Humeres","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyou","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["USA"]},{"name":"Departments of Neurology and Neuroscience, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["USA"]},{"name":"Data Science Institute, Albert Einstein College of Medicine , Bronx, NY 10461 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