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PGC-1α gene transfer restores adhesion and reendothelialization of endothelial progenitor cells from patients with hypertension

Journal of Human Hypertension volume 35, pages 510–516 (2021)Cite this article

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Abstract

Endothelial progenitor cells (EPCs) play an important role in endothelial vascular development and endothelial repair. The upregulation of functional gene expression in EPCs may contribute to the maintenance of EPC-based endothelial repair. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a powerful regulator of mitochondrial biogenesis and antioxidant defense, but its impact on early EPCs remains poorly understood. This study was designed to investigate whether decline in PGC-1α expression impairs in vitro adhesion, migration, and in vivo reendothelialization capacity of early EPCs from patients with hypertension. We engineered an over-expression of PGC-1α within EPCs from hypertensive patients, which were transduced with an adenoviral vector encoding the human PGC-1α gene. Then we tested the migration and adhesion function of EPCs in vitro and endothelium-reparative capacity in vivo with a nude mouse model of carotid artery injury. Our data revealed for the first time that PGC-1α expression of EPCs is lower in hypertensive patients than that in healthy subjects. Meanwhile, the in vitro adhesion and migration function, in vivo endothelial repair capacity of early EPCs were significantly reduced in hypertensive patients compared with normal subjects. Furthermore, PGC-1α gene transfer contributes to increased adhesion in vitro and enhanced endothelium-reparative capacity in vivo of EPCs from hypertensive patients through the augmented expression of PGC-1α. Thus, upregulation of PGC-1α expression of EPCs may be a novel complementary therapeutic target to increase endothelium-reparative capacity in hypertensive patients.

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Fig. 1: Dysfunction and reduced PGC-1α expression of early EPCs in hypertension.
Fig. 2: Effects of Ad5/PGC-1α gene transfer on in vitro functions and in vivo reendothelialization capacity of early EPCs.

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Acknowledgements

The work was supported financially by the National Nature Science Foundation (31530023, 81500205) of China.

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  1. These authors contributed equally: Wenli Xie, Fang Wu

Authors and Affiliations

  1. Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Wenli Xie, Fang Wu, Jiang He, Long Chen, Xiaoyu Zhang, Jiapan Sun, Xing Liu & Jun Tao

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  1. Wenli Xie
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Xie, W., Wu, F., He, J. et al. PGC-1α gene transfer restores adhesion and reendothelialization of endothelial progenitor cells from patients with hypertension. J Hum Hypertens 35, 510–516 (2021). https://doi.org/10.1038/s41371-020-0364-y

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