β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure
| Autor: | Alessandro Cannavo, Seungho Jun, Giuseppe Rengo, Federica Marzano, Jacopo Agrimi, Daniela Liccardo, Andrea Elia, Gizem Keceli, Giovanna G. Altobelli, Lorenzo Marcucci, Aram Megighian, Erhe Gao, Ning Feng, Kai Kammers, Nicola Ferrara, Livio Finos, Walter J. Koch, Nazareno Paolocci |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Circulation Research. 132:867-881 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.122.321583 |
| Popis: | Background: Loss of brain-derived neurotrophic factor (BDNF)/TrkB (tropomyosin kinase receptor B) signaling accounts for brain and cardiac disorders. In neurons, β-adrenergic receptor stimulation enhances local BDNF expression. It is unclear if this occurs in a pathophysiological relevant manner in the heart, especially in the β-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. Methods: 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, β3AR 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). Results: In wild type hearts, BDNF levels rose early after MI ( Conclusions: BDNF loss underscores chronic postischemic heart failure. TrkB agonists can improve ischemic LV dysfunction via replenished myocardial BDNF content. Direct cardiac β3AR stimulation, or β-blockers (via upregulated β3AR), is another BDNF-based means to fend off chronic postischemic heart failure. |
| Databáze: | OpenAIRE |
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