{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:56:38Z","timestamp":1777416998764,"version":"3.51.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The imbalance of monocyte\/macrophage polarization toward the preferential proinflammatory phenotype and a lack of normal inflammation resolution are present in acute myocardial infarction (AMI). Our previous study showed that upregulation of brain\u2010derived neurotrophic factor precursor (proBDNF) in M2\u2010like monocytes may contribute to the proinflammatory response in the Stanford type\u2010A acute aortic dissection. The present study aimed to investigate the role of proBDNF signaling in monocytes\/macrophages in the progress of AMI.<\/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              We observed the upregulation of proBDNF in the proinflammatory monocytes of patients with AMI. The upregulation of proBDNF was also observed in the circulating proinflammatory Ly6C\n              <jats:sup>high<\/jats:sup>\n              monocytes and cardiac F4\/80\n              <jats:sup>+<\/jats:sup>\n              CD86\n              <jats:sup>+<\/jats:sup>\n              macrophages 3\u2009days after AMI in a mice model. To neutralize proBDNF, the mice subjected to AMI were injected intraperitoneally with a monoclonal anti\u2010proBDNF antibody. Echocardiography, 2,3,5\u2010triphenyltetrazolium chloride staining, and positron emission tomography\/computed tomography results demonstrate that monoclonal anti\u2010proBDNF antibody treatment further impaired cardiac functions, increased infarct size, and exacerbated the proinflammatory state. Moreover, the level of proinflammatory Ly6C\n              <jats:sup>high<\/jats:sup>\n              in the blood and F4\/80\n              <jats:sup>+<\/jats:sup>\n              CD86\n              <jats:sup>+<\/jats:sup>\n              in the heart was further increased in monoclonal anti\u2010proBDNF antibody mice. RNA sequencing revealed that matrix metalloprotease\u20109 protein level was dramatically increased, along with the activated proinflammatory\u2010related cytokines. Matrix metalloprotease\u20109 inhibitor treatment attenuated the deteriorated effect of monoclonal anti\u2010proBDNF antibody on cardiac function and infarct areas.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our study shows that endogenous proBDNF in monocytes\/macrophages may exert protective roles in cardiac remodeling after AMI by regulating matrix metalloprotease\u20109 activity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028198","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T11:57:24Z","timestamp":1675857444000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Brain\u2010Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes\/Macrophages After Acute Myocardial 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