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Vascular Biology

Tissue Factor Regulates Microvessel Formation and Stabilization by Induction of CCL2 Expression

Gemma Arderiu, Esther Peña, Rosa Aledo, Oriol Juan-Babot, Lina Badimon
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https://doi.org/10.1161/ATVBAHA.111.233536
Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;ATVBAHA.111.233536
Originally published August 25, 2011
Gemma Arderiu
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Esther Peña
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Rosa Aledo
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Oriol Juan-Babot
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Lina Badimon
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Abstract

Objective—Tissue factor (TF) triggers arterial thrombosis. TF is also able to initiate cellular signaling mechanisms leading to angiogenesis. Because high cardiovascular risk atherosclerotic plaques show significant angiogenesis, our objective was to investigate whether TF is able to trigger and stabilize atherosclerotic plaque neovessel formation.

Methods and Results—In this study, we showed, by real-time confocal microscopy in 3-dimensional basement membrane cocultures, that TF in human microvascular endothelial cells (HMEC-1) and in human vascular smooth muscle cells (HVSMCs) plays an important role in the formation of capillary-like networks. TF silencing in endothelial cells and smooth muscle cells inhibits the formation of tube-like structures with stable phenotype. Using an in vivo model, we observed that TF inhibition in either HMEC-1 or HVSMCs reduced their shared ability to form new capillaries. The phenotypic changes induced by TF silencing were linked to reduced CCL2 expression in endothelial cells. Wound healing and Transwell assays demonstrated that TF-induced release of CCL2 stimulated HVSMC migration to HMEC-1.

Conclusion—Endogenous TF regulates CCL2 production in endothelial cells. Secreted CCL2 mediates the angiogenic effect of TF by recruiting smooth muscle cells toward endothelial cells and facilitates the maturation of newly formed microvessels.

  • angiogenesis
  • atherosclerosis
  • cytokines
  • endothelial function
  • vascular biology
  • Received June 23, 2011.
  • Accepted August 3, 2011.
  • © 2011 American Heart Association, Inc.
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    Tissue Factor Regulates Microvessel Formation and Stabilization by Induction of CCL2 Expression
    Gemma Arderiu, Esther Peña, Rosa Aledo, Oriol Juan-Babot and Lina Badimon
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;ATVBAHA.111.233536, originally published August 25, 2011
    https://doi.org/10.1161/ATVBAHA.111.233536

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    Tissue Factor Regulates Microvessel Formation and Stabilization by Induction of CCL2 Expression
    Gemma Arderiu, Esther Peña, Rosa Aledo, Oriol Juan-Babot and Lina Badimon
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;ATVBAHA.111.233536, originally published August 25, 2011
    https://doi.org/10.1161/ATVBAHA.111.233536
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