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PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system.
Arterioscler Thromb Vasc Biol. 2005 Nov; 25(11):2321-7.AT

Abstract

OBJECTIVE

The importance of PAR-1 in blood vessel development has been demonstrated in knockout mice. As endothelial progenitor cells (EPCs) are involved in postnatal vasculogenesis, we examined whether they express PAR-1 and whether stimulation by the peptide SFLLRN modulates their angiogenic properties.

METHODS AND RESULTS

EPC expanded from human CD34+ cord blood cells expressed PAR-1. PAR-1 activation induced EPC proliferation in a concentration-dependent manner far more potently than that of human umbilical vein endothelial cells. PAR-1 activation also enhanced actin reorganization, promoting both spontaneous migration in a Boyden chamber assay and migration toward SDF-1 and VEGF. As shown by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), EPC stimulation by SFLLRN significantly enhanced the mRNA expression of SDF-1 and its receptor CXCR-4. PAR-1 activation also increased CXCR4 expression on EPC and induced SDF-1 secretion, leading to autocrine stimulation. PAR-1 stimulation by SFLLRN also increased the formation of capillary-like structures by EPC in Matrigel, and this effect was abrogated by anti-CXCR-4, anti-SDF-1, and MEK inhibitor pretreatment.

CONCLUSIONS

Human EPCs express functional PAR-1. PAR-1 activation promotes cell proliferation and CXCR4-dependent migration and differentiation, leading to a proangiogenic effect.

Authors+Show Affiliations

INSERM Unité 428, Hôpital Européen Georges Pompidou (AP-HP), Université Paris V, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16141404

Citation

Smadja, David M., et al. "PAR-1 Activation On Human Late Endothelial Progenitor Cells Enhances Angiogenesis in Vitro With Upregulation of the SDF-1/CXCR4 System." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 11, 2005, pp. 2321-7.
Smadja DM, Bièche I, Uzan G, et al. PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. Arterioscler Thromb Vasc Biol. 2005;25(11):2321-7.
Smadja, D. M., Bièche, I., Uzan, G., Bompais, H., Muller, L., Boisson-Vidal, C., Vidaud, M., Aiach, M., & Gaussem, P. (2005). PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(11), 2321-7.
Smadja DM, et al. PAR-1 Activation On Human Late Endothelial Progenitor Cells Enhances Angiogenesis in Vitro With Upregulation of the SDF-1/CXCR4 System. Arterioscler Thromb Vasc Biol. 2005;25(11):2321-7. PubMed PMID: 16141404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. AU - Smadja,David M, AU - Bièche,Ivan, AU - Uzan,Georges, AU - Bompais,Heidi, AU - Muller,Laurent, AU - Boisson-Vidal,Catherine, AU - Vidaud,Michel, AU - Aiach,Martine, AU - Gaussem,Pascale, Y1 - 2005/09/01/ PY - 2005/9/6/pubmed PY - 2006/1/13/medline PY - 2005/9/6/entrez SP - 2321 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 25 IS - 11 N2 - OBJECTIVE: The importance of PAR-1 in blood vessel development has been demonstrated in knockout mice. As endothelial progenitor cells (EPCs) are involved in postnatal vasculogenesis, we examined whether they express PAR-1 and whether stimulation by the peptide SFLLRN modulates their angiogenic properties. METHODS AND RESULTS: EPC expanded from human CD34+ cord blood cells expressed PAR-1. PAR-1 activation induced EPC proliferation in a concentration-dependent manner far more potently than that of human umbilical vein endothelial cells. PAR-1 activation also enhanced actin reorganization, promoting both spontaneous migration in a Boyden chamber assay and migration toward SDF-1 and VEGF. As shown by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), EPC stimulation by SFLLRN significantly enhanced the mRNA expression of SDF-1 and its receptor CXCR-4. PAR-1 activation also increased CXCR4 expression on EPC and induced SDF-1 secretion, leading to autocrine stimulation. PAR-1 stimulation by SFLLRN also increased the formation of capillary-like structures by EPC in Matrigel, and this effect was abrogated by anti-CXCR-4, anti-SDF-1, and MEK inhibitor pretreatment. CONCLUSIONS: Human EPCs express functional PAR-1. PAR-1 activation promotes cell proliferation and CXCR4-dependent migration and differentiation, leading to a proangiogenic effect. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/16141404/PAR_1_activation_on_human_late_endothelial_progenitor_cells_enhances_angiogenesis_in_vitro_with_upregulation_of_the_SDF_1/CXCR4_system_ L2 - https://www.ahajournals.org/doi/10.1161/01.ATV.0000184762.63888.bd?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -