{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:32:48Z","timestamp":1792290768687,"version":"4.4.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Loss of brain-derived neurotrophic factor (BDNF)\/TrkB (tropomyosin kinase receptor B) signaling accounts for brain and cardiac disorders. In neurons, \u03b2-adrenergic receptor stimulation enhances local BDNF expression. It is unclear if this occurs in a pathophysiological relevant manner in the heart, especially in the \u03b2-adrenergic receptor-desensitized postischemic myocardium. Nor is it fully understood whether and how TrkB agonists counter chronic postischemic left ventricle (LV) decompensation, a significant unmet clinical milestone.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We conducted in vitro studies using neonatal rat and adult murine cardiomyocytes, SH-SY5Y neuronal cells, and umbilical vein endothelial cells. We assessed myocardial ischemia (MI) impact in wild type, \u03b23AR knockout, or myocyte-selective BDNF knockout (myoBDNF KO) mice in vivo (via coronary ligation [MI]) or in isolated hearts with global ischemia-reperfusion (I\/R).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>In wild type hearts, BDNF levels rose early after MI (&lt;24 hours), plummeting at 4 weeks when LV dysfunction, adrenergic denervation, and impaired angiogenesis ensued. The TrkB agonist, LM22A-4, countered all these adverse effects. Compared with wild type, isolated myoBDNF KO hearts displayed worse infarct size\/LV dysfunction after I\/R injury and modest benefits from LM22A-4. In vitro, LM22A-4 promoted neurite outgrowth and neovascularization, boosting myocyte function, effects reproduced by 7,8-dihydroxyflavone, a chemically unrelated TrkB agonist. Superfusing myocytes with the \u03b23AR-agonist, BRL-37344, increased myocyte BDNF content, while \u03b23AR signaling underscored BDNF generation\/protection in post-MI hearts. Accordingly, the \u03b21AR blocker, metoprolol, via upregulated \u03b23ARs, improved chronic post-MI LV dysfunction, enriching the myocardium with BDNF. Last, BRL-37344-imparted benefits were nearly abolished in isolated I\/R injured myoBDNF KO hearts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>BDNF loss underscores chronic postischemic heart failure. TrkB agonists can improve ischemic LV dysfunction via replenished myocardial BDNF content. Direct cardiac \u03b23AR stimulation, or \u03b2-blockers (via upregulated \u03b23AR), is another BDNF-based means to fend off chronic postischemic heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.122.321583","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T16:00:21Z","timestamp":1678291221000},"page":"867-881","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["\u03b23AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure"],"prefix":"10.1161","volume":"132","author":[{"given":"Alessandro","family":"Cannavo","sequence":"first","affiliation":[{"name":"Department of Translational Medical Science (A.C., G.R., F.M., D.L., A.E., N. 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