Bisphosphonate of Zoledronate Has Antiapoptotic Effect on Hypoxia/Reoxygenation Injury in Human Embryonic Stem Cell-Derived Cardiomyocytes Through Trk Signaling Pathway

Autor: Hua Wang, Wen-Shu Zhao, Lin Xu
Rok vydání: 2022
Předmět:
Zdroj: Cell Biochemistry and Biophysics. 80:435-442
ISSN: 1559-0283
1085-9195
Popis: In this work, we investigated the in vitro and in vivo functions of bisphosphonate of zoledronate (Zd) in hypoxia/reoxygenation (H/R) injured human embryonic stem cell-derived cardiomyocytes (hES-CMs). In the in vitro setting, the effects of Zd on hES-CM survival and differentiation were examined. We found that low and medium concentrations (2 µm) of Zd did not induce cell death of hES-CMs. 0.5 µm Zd protected H/R-induced hES-CM apoptosis but did not affect key differentiation proteins, including hcTnl, PECM-1 Cnx43 and Pan-Cadherin. In addition, Zd-induced TrkA/B phosphorylation and promoted VEGF to counter the apoptotic effect of H/R injury. In the in vivo animal model of myocardial infarction, Zd treatment promoted the survival of hES-CMs by inducing PECAM1 and hcTnl. Thus, we concluded that Zd protected H/R-induced hES-CM apoptosis in vitro and promoted hES-CM survival in vivo. These data may facilitate the development of human embryonic stem cells into clinical applications for patients with ischemic heart disease.
Databáze: OpenAIRE
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