Experimental Cardiovascular Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1271-9. doi: 10.1161/ATVBAHA.112.300773. Epub 2013 Apr 18.
Intimal hyperplasia is considered to be a healing response and is a major cause of vessel narrowing after injury, where migration of vascular progenitor cells contributes to pathological events, including transplant arteriosclerosis.
In this study, we used a rat aortic-allograft model to identify the predominant cell types associated with transplant arteriosclerosis and to identify factors important in their recruitment into the graft. Transplantation of labeled adventitial tissues allowed us to identify the adventitia as a major source of cells migrating to the intima. RNA microarrays revealed a potential role for monocyte chemoattractant protein 1 (MCP-1), stromal cell-derived factor 1, regulated on activation, normal T cell expressed and secreted, and interferon-inducible protein 10 in the induced vasculopathy. MCP-1 induced migration of adventitial fibroblast cells. CCR2, the receptor for MCP-1, was coexpressed with CD90, CD44, NG2, or sca-1 on mesenchymal stem cells. In vivo experiments using MCP-1-deficient and CCR2-deficient mice confirmed an important role of MCP-1 in the formation of intimal hyperplasia in a mouse model of vascular injury.
The adventitia is a potentially important cellular source that contributes to intimal hyperplasia, and MCP-1 is a potent chemokine for the recruitment of adventitial vascular progenitor cells to intimal lesions.
内膜增生被认为是一种愈合反应，是损伤后血管狭窄的主要原因，其中血管祖细胞的迁移导致包括移植性动脉硬化在内的病理事件。
在这项研究中，我们使用大鼠主动脉同种异体移植模型来确定与移植性动脉硬化相关的主要细胞类型，并确定其招募到移植物中的重要因素。标记的外膜组织的移植使我们能够确定外膜是迁移到内膜的细胞的主要来源。RNA 微阵列揭示了单核细胞趋化蛋白 1 (MCP-1)、基质细胞衍生因子 1、激活调节正常 T 细胞表达和分泌、干扰素诱导蛋白 10 在诱导性血管病变中的潜在作用。MCP-1 诱导外膜成纤维细胞的迁移。CCR2 是 MCP-1 的受体，与间质干细胞上的 CD90、CD44、NG2 或 sca-1 共表达。使用 MCP-1 缺陷型和 CCR2 缺陷型小鼠的体内实验证实了 MCP-1 在血管损伤小鼠模型中形成内膜增生中的重要作用。
外膜是一种潜在的重要细胞来源，有助于内膜增生，MCP-1 是招募外膜血管祖细胞到内膜病变的有效趋化因子。
