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

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Abstract

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.

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Original data were available upon request.

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Author notes

  1. These authors contributed equally: Hua Wang, Wen-Shu Zhao

Authors and Affiliations

  1. Heart Center and Beijing Key Laboratory of Hypertension Research, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

    Hua Wang, Wen-Shu Zhao & Lin Xu

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  1. Hua Wang
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  2. Wen-Shu Zhao
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Contributions

Conceptualization: LX; Methodology: LX Validation: LX; Formal analysis and investigation: HW, WZ; Writing—original draft preparation: HW; Writing—review and editing: LX; Resources: LX, Supervision: LX.

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Correspondence to Lin Xu.

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Wang, H., Zhao, WS. & Xu, L. Bisphosphonate of Zoledronate Has Antiapoptotic Effect on Hypoxia/Reoxygenation Injury in Human Embryonic Stem Cell-Derived Cardiomyocytes Through Trk Signaling Pathway. Cell Biochem Biophys 80, 435–442 (2022). https://doi.org/10.1007/s12013-021-01031-7

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