Arciniegas Enrique, Becerra Aniuska, De Sanctis Juan B, Graterol Armando, Ramírez Richard
Laboratorio de Microscopía Electrónica, Servicio Autónomo Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
Anat Rec A Discov Mol Cell Evol Biol. 2003 Oct;274(2):942-51. doi: 10.1002/ar.a.10105.
Endothelial-mesenchymal transdifferentiation (EMT) is believed to play a crucial role in embryonic vascular development and intimal thickening, which contributes to the pathogenesis of atherosclerotic lesions. However, the mechanisms by which it occurs, as well as the signals that control it, have not yet been elucidated. Given the important role played by the CD40-CD40 ligand (CD40L) system during the initiation and progress of atherosclerosis, we investigated whether both CD40 and CD40L were present in the aortic wall during EMT and the advanced stages of chicken embryo development. CD40-CD40L expression was found on endothelial cells (ECs), mesenchymal cells, and smooth muscle cells (SMCs) at all stages examined, and appeared to be distributed across the aortic wall. However, some notable differences between the expression patterns were observed. CD40 had a more restricted distribution compared to CD40L, and did not stain every cell type of the aortic wall. According to immunoblotting and enzyme-linked immunosorbent assay (ELISA) analyses, the CD40L content was highest at day 7 of development. An important and novel finding was the expression of CD40L in areas where ECs transdifferentiate into mesenchymal cells. Specifically, CD40L was associated to the surface of cells that were detaching and migrating from the monolayer of ECs, whereas for CD40 a very diffuse subcellular localization was seen at the monolayer and the detaching and migrating cells. These data suggest a possible role for CD40-CD40L interactions during EMT and the remodeling of the aorta.
内皮-间充质转分化（EMT）被认为在胚胎血管发育和内膜增厚中起关键作用，而内膜增厚会促进动脉粥样硬化病变的发病机制。然而，其发生机制以及控制它的信号尚未阐明。鉴于CD40-CD40配体（CD40L）系统在动脉粥样硬化的发生和发展过程中发挥的重要作用，我们研究了在鸡胚发育的EMT阶段和晚期，主动脉壁中是否同时存在CD40和CD40L。在所检查的所有阶段，在内皮细胞（ECs）、间充质细胞和平滑肌细胞（SMCs）上均发现了CD40-CD40L表达，且似乎分布于整个主动脉壁。然而，观察到表达模式存在一些显著差异。与CD40L相比，CD40的分布更为局限，且并非对主动脉壁的每种细胞类型都进行染色。根据免疫印迹和酶联免疫吸附测定（ELISA）分析，CD40L含量在发育第7天时最高。一个重要且新颖的发现是，在ECs转分化为间充质细胞的区域有CD40L表达。具体而言，CD40L与从EC单层脱离并迁移的细胞表面相关，而对于CD40，在单层以及脱离和迁移的细胞中可见非常弥散的亚细胞定位。这些数据表明CD40-CD40L相互作用在EMT和主动脉重塑过程中可能发挥作用。
