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Role of Mydgf in the regulation of hypoxia/reoxygenation-induced apoptosis in cardiac microvascular endothelial cells

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Abstract

We aimed to explore the effects of myeloid-derived growth factor (Mydgf) on the regulation of hypoxia/reoxygenation (HR)–induced apoptosis of cardiac microvascular endothelial cells (CMECs). CMECs were exposed to hypoxia for 24 h and reoxygenation for 6 h to establish an HR cell model. Subsequently, an adenovirus was used to overexpress Mydgf in CMECs. Flow cytometry and TUNEL staining were used to detect the extent of apoptosis, whereas qPCR was used to detect the relative expression of Mydgf mRNA. Western blotting was also performed to detect the expression of apoptosis-related proteins and endoplasmic reticulum stress (ERS)–related proteins, including C/EBP Homologous Protein (CHOP), glucose-regulated protein 78 (GRP 78), and cleaved Caspase-12. The endoplasmic reticulum stress agonist tunicamycin (TM) was used to stimulate CMECs for 24 h as a rescue experiment for Mydgf. Flow cytometry revealed that the HR model effectively induced endothelial cell apoptosis, whereas qPCR and western blotting showed that Mydgf mRNA and protein levels decreased significantly after HR treatment (P < 0.05). Overexpression of Mydgf in cells effectively reduced apoptosis after HR. Furthermore, western blotting showed that HR induced a significant upregulation of CHOP, GRP78, and cleaved-Caspase-12 expression in CMECs, whereas HR-treated cells downregulated the expression of CHOP, GRP78, and cleaved-Caspase-12 after Mydgf overexpression. Under HR conditions, TM significantly reversed the protective effect of Mydgf on CMECs. Mydgf may reduce CMEC apoptosis induced by HR by regulating oxidative stress in ERS.

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The data used to support the findings of this study are included within the article.

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Funding

This study was supported by a scientific research project from the National Natural Science Foundation of China (Grant Nos. 81860061 and 82160057). This work was also supported by the Guizhou Science and Technology Foundation (ZK[2021]353).

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  1. Yan Wang and Yu Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China

    Yan Wang, Yu Zhang, Jiao Li, Ranzun Zhao, Xianping Long, Chaofu Li, Weiwei Liu, Wenming Chen & Bei Shi

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  1. Yan Wang
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  2. Yu Zhang
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  3. Jiao Li
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  7. Weiwei Liu
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  9. Bei Shi
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Contributions

Yan Wang and Bei Shi conceived and designed the experiments;

Yu Zhang and Jiao Li performed the experiments;

Ranzhun Zhao and Xianping Long analyzed the data;

Chaofu Li, Weiwei Liu, and Wenming Chen prepared figures;

Yan Wang drafted the paper;

Bei Shi revised the paper.

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Correspondence to Bei Shi.

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The authors declare no competing interests.

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Wang, Y., Zhang, Y., Li, J. et al. Role of Mydgf in the regulation of hypoxia/reoxygenation-induced apoptosis in cardiac microvascular endothelial cells. In Vitro Cell.Dev.Biol.-Animal 58, 669–678 (2022). https://doi.org/10.1007/s11626-022-00709-3

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  • DOI: https://doi.org/10.1007/s11626-022-00709-3

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