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CCN1 promotes the differentiation of endothelial progenitor cells and reendothelialization in the early phase after vascular injury

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Abstract

Endothelial progenitor cells (EPCs) contribute to the process of reendothelialization and prevent neointimal formation after vascular injury. The present study was designed to investigate whether the cysteine-rich 61 (CYR61, CCN1), an important matricellular component of local vascular microenvironment, has effect on EPCs differentiation and reendothelialization in response to vascular injury in rat. Following balloon injury, CCN1 was rapidly induced and dynamically changed at vascular lesions. Overexpression of CCN1 by adenovirus (Ad-CCN1) accelerated reendothelialization and inhibited neointimal formation in the early phase (day 14) after vascular injury (p < 0.05), while no effect was shown on day 21. Ad-CCN1 treatment increased the adhering EPCs on the surface of injured vessels on day 7, and the ratio of GFP- and vWF-positive area to the total luminal length on day 14 was 2.3-fold higher in the Ad-CCN1-EPC-transplanted group than in controls. Consistent with these findings, CCN1-stimulated EPC differentiation in vitro and 20 genes were found differentially expressed during CCN1-induced EPC differentiation, including Id1, Vegf-b, Vegf-c, Kdr, Igf-1, Ereg, Tgf, Mdk, Ptn, Timp2, etc. Among them, negative transcriptional regulator Id1 was associated with CCN1 effect on EPC differentiation. Our data suggest that CCN1, from the microenvironment of injured vessels, enhances reendothelialization via a direct action on EPC differentiation, revealing a possible new mechanism underlying the process of vascular repair.

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Acknowledgments

Appreciation goes to Dr. Jun Wang for his encouragement and kind help in this work. These studies were supported in part by the National Natural Science Foundation of China (grant 30770852, 81000070) and Chongqing Municipal Natural Science Foundation (grant 2007BB5028).

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Authors and Affiliations

  1. Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Yang Yu, Jun Qin, Chun-Yan Kuang, Ming-Bao Song, Shi-Yong Yu, Bin Cui, Jian-Fei Chen & Lan Huang

  2. Department of Rehabilitation, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Yu Gao

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  1. Yang Yu
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Correspondence to Lan Huang.

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Yu, Y., Gao, Y., Qin, J. et al. CCN1 promotes the differentiation of endothelial progenitor cells and reendothelialization in the early phase after vascular injury. Basic Res Cardiol 105, 713–724 (2010). https://doi.org/10.1007/s00395-010-0117-0

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  • DOI: https://doi.org/10.1007/s00395-010-0117-0

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