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High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy

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Abstract

Background

Pulmonary hypertension (PH) is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Endothelial progenitor cells (EPCs) have been proved to be a potential therapeutic strategy to treat PH. Autophagy has been found to be protective to hypoxia-induced PH. In this study, we applied high shear stress (HSS)-induced PH, and examined whether EPCs confer resistance against HSS-induced PH through autophagy.

Methods

Pulmonary microvascular endothelial cells (PMVECs) were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition. Levels of p62, a selective autophagy substrate, were quantified by western blotting. Cell viability was determined by trypan blue exclusion test.

Results

The p62 level in PMVECs was increased at 4 hours after HSS, peaked at 12 hours and declined at 24 hours. The cell viability gradually decreased. Compared with PMVECs cultured by empty medium, in cells cultured by EPC-conditioned medium (EPC-CM), the cell viability was significantly higher; however, p62 levels were also significantly higher, suggesting inhibition of autophagy by EPC-CM. Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH.

Conclusions

EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH. However, suppression of autophagy leads to cell death. EPCs could fight against PH through cellular or molecular pathways independent of autophagy. But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Children’s Hospital, Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou, 310051, China

    Bi-Jun Xu, Xi-Wang Liu, Shu Fang & Qiang Shu

  2. Department of Cardiothoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China

    Bi-Jun Xu

  3. The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China

    Jian Chen

  4. Central Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China

    Xi Chen

  5. Department of SICU, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China

    Lei Hu, Shan-Shan Shi, Li-Zhong Du & Lin-Hua Tan

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  1. Bi-Jun Xu
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  2. Jian Chen
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  3. Xi Chen
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  5. Shu Fang
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  7. Lei Hu
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  9. Li-Zhong Du
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  10. Lin-Hua Tan
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Correspondence to Lin-Hua Tan.

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Cite this article

Xu, BJ., Chen, J., Chen, X. et al. High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy. World J Pediatr 11, 171–176 (2015). https://doi.org/10.1007/s12519-015-0008-4

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  • DOI: https://doi.org/10.1007/s12519-015-0008-4

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