Neuregulin-1 (Nrg-1) is a growth factor produced by endothelial cells, necessary for a correct cardiac development. In adult heart Nrg-1 mediates different cellular processes including cell survival and proliferation as well as glucose uptake on cardiomyocytes that express ErbB receptors. For its role, Nrg-1 has been proposed as a potential drug for heart failure, and numerous in vivo studies demonstrated that Nrg-1 treatment improves myocardial function and survival in ischemic model throught PI3K/AKT pathway. Nevertheless, it is still not clear which ErbB receptor is activated by Nrg-1 to exert its beneficial effects in post-ischemic phase. Most of the studies were focused on the pathways activated by ErbB2 and ErbB4, although few years ago it has been shown that also ErbB3 is expressed by adult cardiomyocytes. To better understand the involvement of the different ErbB receptors in heart failure, we performed a pilot analysis of ErbB expression on post-ischemic heart. We used the ex vivo Langendorff model to induce ischemia/reperfusion (I/R) injury in rat heart and we analysed the mRNA expression of Nrg-1 and ErbBs after two hours from injury by quantitative real-time PCR. We observed an increase of ErbB3 transcription in I/R hearts compared to the sham hearts, whereas no changes occur for ErbB2 and ErbB4, and Nrg-1 is barely detectable. Interestingly, ErbB3 up-regulation was also observed in infarcted hearts subjected to post-conditioning, a protective procedure that can decrease infarct size. Altogether, our results demonstrate that Nrg-1 receptor ErbB3, and not ErbB2 and ErbB4, is upregulated in post-ischemic myocardium suggesting that heart protection exerted by Nrg-1 might be mainly mediated by ErbB3-related signaling possibly through the PI3K-AKT pathway.

NRG-1 RECEPTOR ERBB3, AND NOT ERBB2 AND ERBB4, IS UP-REGULATED AFTER EX-VIVO MYOCARDIAL INFARCTION, WITH OR WITHOUT POST-CONDITIONING PROTECTION

MORANO, MICHELA;ANGOTTI, CARMELINA;TULLIO, FRANCESCA;GAMBAROTTA, Giovanna;PENNA, Claudia;PAGLIARO, Pasquale;GEUNA, Stefano
2014-01-01

Abstract

Neuregulin-1 (Nrg-1) is a growth factor produced by endothelial cells, necessary for a correct cardiac development. In adult heart Nrg-1 mediates different cellular processes including cell survival and proliferation as well as glucose uptake on cardiomyocytes that express ErbB receptors. For its role, Nrg-1 has been proposed as a potential drug for heart failure, and numerous in vivo studies demonstrated that Nrg-1 treatment improves myocardial function and survival in ischemic model throught PI3K/AKT pathway. Nevertheless, it is still not clear which ErbB receptor is activated by Nrg-1 to exert its beneficial effects in post-ischemic phase. Most of the studies were focused on the pathways activated by ErbB2 and ErbB4, although few years ago it has been shown that also ErbB3 is expressed by adult cardiomyocytes. To better understand the involvement of the different ErbB receptors in heart failure, we performed a pilot analysis of ErbB expression on post-ischemic heart. We used the ex vivo Langendorff model to induce ischemia/reperfusion (I/R) injury in rat heart and we analysed the mRNA expression of Nrg-1 and ErbBs after two hours from injury by quantitative real-time PCR. We observed an increase of ErbB3 transcription in I/R hearts compared to the sham hearts, whereas no changes occur for ErbB2 and ErbB4, and Nrg-1 is barely detectable. Interestingly, ErbB3 up-regulation was also observed in infarcted hearts subjected to post-conditioning, a protective procedure that can decrease infarct size. Altogether, our results demonstrate that Nrg-1 receptor ErbB3, and not ErbB2 and ErbB4, is upregulated in post-ischemic myocardium suggesting that heart protection exerted by Nrg-1 might be mainly mediated by ErbB3-related signaling possibly through the PI3K-AKT pathway.
2014
Forum “NEW ROADS IN CARDIOVASCULAR RESEARCH”
Pisa, Aula Magna Scuola Superiore Sant’Anna
13/10/2014
2 nd Workshop on New Roads in Cardiovascular Research
17
17
http://www.sirc-cardio.it/
Ischemia/reperfusion; ErbB; Cardioprotection; Postconditioning
Morano M; Angotti C; Tullio F; Gambarotta G; Penna C; Pagliaro P; Geuna S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/156098
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