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Fluid Shear Stress Ameliorates Prehypertension-Associated Decline in Endothelium-Reparative Potential of Early Endothelial Progenitor Cells

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Abstract

This study investigated the effects of prehypertension and shear stress on the reendothelialization potential of human early EPCs and explored its potential mechanisms. Early EPCs from the prehypertensive patients showed reduced migration and adhesion in vitro and demonstrated a significantly impaired in vivo reendothelialization capacity. Shear stress pretreatment markedly promoted the in vivo reendothelialization capacity of EPCs. Although basal CXCR4 expression in early EPCs from prehypertensive donors was similar to that from healthy control, SDF-1-induced phosphorylation of CXCR4 was lower in prehypertensive EPCs. Shear stress up-regulated CXCR4 expression and increased CXCR4 phosphorylation, and restored the SDF-1/CXCR4-dependent JAK-2 phosphorylation in prehypertensive EPCs. CXCR4 knockdown or JAK-2 inhibitor treatment prevents against shear stress-induced increase in the migration, adhesion and reendothelialization capacity of the prehypertensive EPCs. Collectively, CXCR4 receptor profoundly modulates the reendothelialization potential of early EPCs. The abnormal CXCR4-mediated JAK-2 signaling may contribute to impaired functions of EPCs from patients with prehypertension.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81700263, No. 81370309 and No. 82100348); the Basic and Applied Basic Research Foundation of Guangdong Province of China (No. 2020A1515110865); Funding by Science and Technology Projects in Guangzhou City of China (No. 202102021124). This project was also supported by a grant from the Medical Science Technology Research Foundation of Guangdong Province of China (No. B2021162).

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Author notes

  1. Qingsong Hu, Xiaobian Dong and Kun Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, First Affiliated Hospital of Jinan University, NO.603, Huangpu Big Road, Tianhe District, Guangzhou City, 510630, China

    Qingsong Hu, Xiaobian Dong, Tao Zhang, Jianyi Feng, Hairui Li & Xiaoming Chen

  2. Department of Cardiology, Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China

    Kun Zhang, Yangxin Chen & Ruqiong Nie

  3. Department of Cardiology, The Guangzhou Eighth People’s Hospital, Guangzhou Medical University, NO.8 Huaying road, Baiyun district, Guangzhou city, 510000, Guangdong, China

    Huangfeng Song, Cuizhi Li & Youbin Liu

  4. Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China

    Xiao Ke

  5. Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen, 518057, China

    Xiao Ke

Authors
  1. Qingsong Hu
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Contributions

Y.L. and X.C. conceived and designed research; Q.H., X.D. and K.Z. performed experiments; Q.H., T.Z., J.F., X.K., H.L. and Y.C. analyzed data; H.S., C.L., T.Z., J.F., X.K., H.L. and R.N. interpreted results of experiments; Q.H., X.D., K.Z., H.S., C.L., T.Z., J.F., X.K., H.L., Y.C., R.N., X.C. and Y.L. approved final version of manuscript.

Corresponding authors

Correspondence to Xiaoming Chen or Youbin Liu.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Associate Editor Nicola Smart oversaw the review of this article

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Supplementary Information

Figure S1:

Shear stress enhanced CXCR4 expression in EPCs. A and C. Representative images and quantification of CXCR4 mRNA expression detected by RT-PCR (A) and total CXCR4 protein expression detected by West blot analysis (C) in EPCs treated with 15 dyn/cm2 shear stress for durations as indicated (*P < 0.05 vs. static healthy EPCs; #P < 0.05 vs. static prehypertensive EPCs; n = 5). B and D. Representative images and quantification of CXCR4 mRNA expression detected by RT-PCR (B) and total CXCR4 protein expression by West blot analysis (D) in EPCs treated for 12 h with different doses of shear stress as indicated (*P < 0.05 vs. static healthy EPCs; # P < 0.05 vs. static prehypertensive EPCs; n = 5). (PNG 1839 kb)

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Hu, Q., Dong, X., Zhang, K. et al. Fluid Shear Stress Ameliorates Prehypertension-Associated Decline in Endothelium-Reparative Potential of Early Endothelial Progenitor Cells. J. of Cardiovasc. Trans. Res. 15, 1049–1063 (2022). https://doi.org/10.1007/s12265-022-10235-y

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