Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo
Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo
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DOI：
10.1172/jci24340
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发表时间：
2006-06-01
影响因子：
15.9
通讯作者：
Wagener, Christoph
中科院分区：
文献类型：
--
作者：
Horst, Andrea Kristina;Ito, Wulf D.;Wagener, Christoph
癌胚抗原相关细胞粘附分子1（CEACAM 1）是IG超家族的一种细胞粘附分子，与血管生成的早期阶段相关。在体外，CEACAM 1调节鼠内皮细胞的增殖、迁移和分化。为了证明CEACAM 1在功能上参与体内血管重塑的调节，我们分析了2种不同的遗传模型：在Ceacam 1（-/-）小鼠中，Ceacam 1基因被系统性删除，而在CEACAM 1（endo+）小鼠中，CEACAM 1在Tie 2受体酪氨酸激酶的内皮细胞特异性启动子的控制下过表达。在基质胶塞试验中，Ceacam 1（-/-）小鼠未能建立新的毛细血管，而在CEACAM 1（endo+）小鼠中，植入物广泛血管化。通过股动脉结扎诱导后肢缺血后，与WT同窝小鼠相比，Ceacam 1（-/-）小鼠的小动脉和侧支血流生长显著减少。与CEACAM 1在血管重塑中的因果作用一致，CEACAM 1（endo+）小鼠在动脉闭塞后表现出血管再生和侧支血流的增加。我们的研究结果表明，CEACAM 1的表达是重要的建立新形成的血管在体内。因此，CEACAM 1可能是疾病中血管生成治疗操作的未来靶点。
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 CEACAM1(endo+) 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 CEACAM1(endo+) 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, CEACAM1(endo+) 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.