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01.05.2019 | Original Contribution

Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury

verfasst von: Hsing-Hui Su, Jiuan-Miaw Liao, Yi-Hsin Wang, Ke-Min Chen, Chia-Wei Lin, I-Hui Lee, Yi-Ju Li, Jing-Yang Huang, Shen Kou Tsai, Jiin-Cherng Yen, Shiang-Suo Huang

Erschienen in: Basic Research in Cardiology | Ausgabe 3/2019

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Abstract

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-β1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia–reperfusion (I–R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I–R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I–R injury and investigate the underlying mechanism in Sprague–Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I–R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-β signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-β signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I–R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I–R injury.

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Titel: Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury
verfasst von: Hsing-Hui Su
Jiuan-Miaw Liao
Yi-Hsin Wang
Ke-Min Chen
Chia-Wei Lin
I-Hui Lee
Yi-Ju Li
Jing-Yang Huang
Shen Kou Tsai
Jiin-Cherng Yen
Shiang-Suo Huang
Publikationsdatum: 01.05.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 3/2019
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-019-0728-z

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Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury

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