Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
复制标题
内皮 TGF-β 信号传导驱动血管炎症和动脉粥样硬化
DOI：
10.1038/s42255-019-0102-3
复制
发表时间：
2019-09-01
影响因子：
20.8
通讯作者：
Simons, Michael
中科院分区：
文献类型：
--
作者：
Chen, Pei-Yu;Qin, Lingfeng;Simons, Michael
动脉粥样硬化是一种进行性血管疾病，由异常剪切应力和内皮脂质潴留之间的相互作用触发。这些因素和潜在的其他因素的组合导致血管壁中的慢性炎症反应，这被认为是导致以动脉粥样硬化斑块的积聚为特征的疾病进展的原因。然而，负责维持斑块炎症和斑块生长的分子事件尚未完全确定。在这里，我们发现内皮转化生长因子β（TGF-β）信号是动脉粥样硬化相关血管炎症的主要驱动因素之一。在高脂血症小鼠中抑制内皮TGF-β信号传导可减少血管壁炎症和血管通透性，并导致疾病进展的停滞和已建立病变的消退。内皮TGF-β信号传导的这些促炎作用与其在其他细胞类型中的作用形成鲜明对比，并将其鉴定为动脉粥样硬化斑块生长的重要驱动因素，并显示了旨在控制这种疾病的细胞类型特异性治疗干预的潜力。
Atherosclerosis is a progressive vascular disease triggered by interplay between abnormal shear stress and endothelial lipid retention. A combination of these and, potentially, other factors leads to a chronic inflammatory response in the vessel wall, which is thought to be responsible for disease progression characterized by a buildup of atherosclerotic plaques. Yet molecular events responsible for maintenance of plaque inflammation and plaque growth have not been fully defined. Here we show that endothelial transforming growh factor beta (TGF-beta) signalling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGF-beta signalling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. These proinflammatory effects of endothelial TGF-beta signalling are in stark contrast with its effects in other cell types and identify it as an important driver of atherosclerotic plaque growth and show the potential of cell-type-specific therapeutic intervention aimed at control of this disease.