Department of Infection, Immunity & Cardiovascular Disease (IICD), Faculty of Medicine, Dentistry & Health, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.
Laboratory for Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ Groningen, The Netherlands.
Cardiovasc Res. 2018 Mar 15;114(4):565-577. doi: 10.1093/cvr/cvx253.
Atherosclerosis is an inflammatory disease resulting in the hardening and thickening of the wall of arteries and the formation of plaques, which comprise immune cells, mesenchymal cells, lipids, and extracellular matrix. The source of mesenchymal cells in the atherosclerotic plaques has been under scrutiny for years. Current endothelial-lineage tracing studies indicate that the endothelium is a source for plaque-associated mesenchymal cells. Endothelial cells can acquire a mesenchymal phenotype through endothelial-mesenchymal transition (EndMT), wherein the expression of endothelial markers and functions is lost and the expression of mesenchymal cell marker and functions acquired. Furthermore, EndMT can result in delamination and migration of endothelial cell-derived mesenchymal cells into the underlying tissue. Here, we review the contribution of EndMT in vascular disease focusing on atherosclerosis and describe the major biochemical and biomechanical signalling pathways in EndMT during atherosclerosis progression. Furthermore, we address how the well-established systemic atherosclerosis risk factors might facilitate EndMT during atherosclerosis.
动脉粥样硬化是一种炎症性疾病，导致动脉壁变硬变厚，并形成斑块，斑块由免疫细胞、间充质细胞、脂质和细胞外基质组成。多年来，人们一直在研究动脉粥样硬化斑块中间充质细胞的来源。目前的内皮谱系示踪研究表明，内皮细胞是斑块相关间充质细胞的来源。内皮细胞可以通过内皮-间充质转化（EndMT）获得间充质表型，其中内皮标记物和功能的表达丢失，而间充质细胞标记物和功能的表达获得。此外，EndMT 可导致内皮细胞衍生的间充质细胞从内皮层分离和迁移到下面的组织中。在这里，我们回顾了 EndMT 在血管疾病（特别是动脉粥样硬化）中的作用，并描述了动脉粥样硬化进展过程中 EndMT 的主要生化和生物力学信号通路。此外，我们还探讨了已确立的系统性动脉粥样硬化危险因素如何在动脉粥样硬化过程中促进 EndMT。
