{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:02Z","timestamp":1790278802467,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Myocardial infarction (MI) is characterized by the emergence of dead or dying cardiomyocytes and excessive immune cell infiltration after coronary vessel occlusion. However, the complex transcriptional profile, pathways, cellular interactome, and transcriptional regulators of immune subpopulations after MI remain elusive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Here, male C57BL\/6 mice were subjected to MI surgery and monitored for 1 day and 7\u2009days, or sham surgery for 7\u2009days, then cardiac CD45\u2010positive immune cells were collected for single\u2010cell RNA sequencing to determine immune heterogeneity. A total of 30\u2009135 CD45\n              <jats:sup>+<\/jats:sup>\n              immune cells were partitioned into macrophages, monocytes, neutrophils, dendritic cells, and T or B cells for further analysis. We showed that macrophages enriched for Olr1 and differentially expressed Gpnmb represented 2 crucial ischemia\u2010associated macrophages with distinct proinflammatory and prophagocytic capabilities. In contrast to the proinflammatory subset of macrophages enriched for Olr1, Gpnmb\u2010positive macrophages exhibited higher phagocytosis and fatty acid oxidation preference, which could be abolished by etomoxir treatment. In addition to macrophages, MI triggered prompt recruitment of neutrophils into murine hearts, which constituted the sequential cell\u2010fate from na\u00efve S100a4\u2010positive, to activated Sell\u2010high, to aging Icam1\u2010high neutrophils. In silico tools predicted that the excessively expanded neutrophils at 1 day were attributed to chemokine C\u2010C motif ligand\/chemokine C\u2010X\u2010C motif ligand pathways, whereas CD80\/inducible T\u2010cell costimulator (ICOS) signaling was responsible for the immunosuppressive response at day 7 after MI. Finally, the Fos\/AP\u20101 (activator protein 1) regulon was identified as the critical regulator of proinflammatory responses, which was significantly activated in patients with dilated cardiomyopathy and ischemic cardiomyopathy. We showed the enriched Fos\/AP\u20101 target gene loci in genome\u2010wide association study signals for coronary artery diseases and MI. Targeting Fos\/AP\u20101 with the selective inhibitor T5224 blunted leukocyte infiltration and alleviated cardiac dysfunction in the preclinical murine MI model.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Taken together, this single\u2010cell RNA sequencing data lay the groundwork for the understanding of immune cell heterogeneity and dynamics in murine ischemic hearts. Moreover, Fos\/AP\u20101 inhibition mitigates inflammatory responses and cardiac dysfunction, which might provide potential therapeutic benefits for heart failure intervention after MI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027228","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T11:38:50Z","timestamp":1671017930000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Global Characteristics and Dynamics of Single Immune Cells After Myocardial Infarction"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-3202","authenticated-orcid":false,"given":"Lingfang","family":"Zhuang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai PR China"},{"name":"Institute of Cardiovascular Diseases Shanghai Jiao Tong University School 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