Carcinoembryonic antigen–related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo
Andrea Kristina Horst, … , Nicole Beauchemin, Christoph Wagener
Andrea Kristina Horst, … , Nicole Beauchemin, Christoph Wagener
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1596-1605. https://doi.org/10.1172/JCI24340.
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Research Article Vascular biology

Carcinoembryonic antigen–related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo

Abstract

Carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1), a cellular adhesion molecule of the Ig superfamily, is associated with early stages of angiogenesis. In vitro, CEACAM1 regulates proliferation, migration, and differentiation of murine endothelial cells. To prove that CEACAM1 is functionally involved in the regulation of vascular remodeling in vivo, we analyzed 2 different genetic models: in Ceacam1–/– mice, the Ceacam1 gene was deleted systemically, and in CEACAM1endo+ mice, CEACAM1 was overexpressed under the control of the endothelial cell–specific promoter of the Tie2 receptor tyrosine kinase. In Matrigel plug assays, Ceacam1–/– mice failed to establish new capillaries whereas in CEACAM1endo+ mice the implants were vascularized extensively. After induction of hind limb ischemia by femoral artery ligation, Ceacam1–/– mice showed significantly reduced growth of arterioles and collateral blood flow compared with their WT littermates. In agreement with a causal role of CEACAM1 in vascular remodeling, CEACAM1endo+ mice exhibited an increase in revascularization and collateral blood flow after arterial occlusion. Our findings indicate that CEACAM1 expression is important for the establishment of newly formed vessels in vivo. Hence CEACAM1 could be a future target for therapeutic manipulation of angiogenesis in disease.

Authors

Andrea Kristina Horst, Wulf D. Ito, Joachim Dabelstein, Udo Schumacher, Heike Sander, Claire Turbide, Jens Brümmer, Thomas Meinertz, Nicole Beauchemin, Christoph Wagener

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Figure 3

Aortic ring assays of CEACAM1endo+ and Ceacam1–/– mice.

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Aortic ring assays of CEACAM1endo+ ...
(A) Aortic ring assays of Ceacam1–/– mice, CEACAM1endo+ transgenic animals, and their WT littermates. Aortas were cut into 1-mm-thick rings, implanted into Matrigel, and allowed to grow for 10 days. Images were taken on day 8, and endothelial cell tube formation and tubular branching into capillary-like networks were compared. In Ceacam1–/– mice, the capillary network exhibited lower complexity compared with the branched pseudovascular trees in CEACAM1endo+ mice, FVB/N WT, and C57BL/6 WT mice. Arrows show the lack of connection among neighboring protrusions. Magnification, ×100, ×200 (insets). (B and C) Aortic ring assays were performed from at least 6 CEACAM1endo+ and WT littermates, and the overall length of endothelial cell sprouts (B) and the overall number of endothelial cell sprouts emerging from the aortic ring (C) were determined. The invasion length of capillary tubes formed by CEACAM1endo+ significantly exceeded that of their WT littermates on days 4, 6, and 8. Significant differences in numbers of endothelial cell tubes were obtained on day 4 of the assay. *P < 0.05; **P < 0.01. (D and E) Aortic ring assays were performed from at least 6 Ceacam1–/– and WT littermates, and the number of endothelial cell sprouts per aortic ring (D) and the overall length of capillary protrusions in aortic explants (E) were determined. The number of endothelial protrusions per aortic ring in Ceacam1–/– mice was significantly different compared with WT mice on days 4, 6, and 8. No significant differences in the length of the endothelial pseudotubes were detected.