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原发性纤毛与动脉粥样硬化

Primary Cilia and Atherosclerosis.

作者信息

Wang Zhi-Mei, Gao Xiao-Fei, Zhang Jun-Jie, Chen Shao-Liang

机构信息

Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Front Physiol. 2021 Feb 2;12:640774. doi: 10.3389/fphys.2021.640774. eCollection 2021.

Abstract

In artery tree, endothelial function correlates with the distribution of shear stress, a dragging force generated by flowing blood. In laminar shear stress areas, endothelial cells (ECs) are available to prevent atherosclerosis, however, ECs in disturbed shear stress sites are featured with proinflammation and atherogenesis. Basic studies in the shear stress field that focused on the mechanosensors of ECs have attracted the interest of researchers. Among all the known mechanosensors, the primary cilium is distinctive because it is enriched in disturbed shear stress regions and sparse in laminar shear stress areas. The primary cilium, a rod liked micro-organelle, can transmit extracellular mechanical and chemical stimuli into intracellular space. In the cardiovascular system, primary cilia are enriched in disturbed shear stress regions, where blood flow is slow and oscillatory, such as the atrium, downstream of the aortic valve, branches, bifurcations, and inner curves of the artery. However, in the atrioventricular canal and straight vessels, blood flow is laminar, and primary cilia can barely be detected. Primary cilia in the heart cavity prevent ECs from mesenchymal transition and calcification by suppressing transforming growth factor (TGF) signaling. Besides, primary cilia in the vascular endothelium protected ECs against disturbed shear stress-induced cellular damage by triggering Ca influx as well as nitric oxide (NO) release. Moreover, primary cilia inhibit the process of atherosclerosis. In the current review, we discussed ciliogenesis, ciliary structure, as well as ciliary distribution, function and the coordinate signal transduction with shear stress in the cardiovascular system.

摘要

在动脉树中,内皮功能与剪切应力的分布相关,剪切应力是由流动的血液产生的一种拖曳力。在层流剪切应力区域,内皮细胞(ECs)有助于预防动脉粥样硬化,然而,处于紊乱剪切应力部位的内皮细胞具有促炎和动脉粥样硬化形成的特征。剪切应力领域中专注于内皮细胞机械传感器的基础研究吸引了研究人员的兴趣。在所有已知的机械传感器中,初级纤毛很独特,因为它在紊乱剪切应力区域富集,而在层流剪切应力区域稀疏。初级纤毛是一种杆状的微细胞器,可将细胞外的机械和化学刺激传递到细胞内空间。在心血管系统中,初级纤毛在紊乱剪切应力区域富集,这些区域血流缓慢且呈振荡状,如心房、主动脉瓣下游、分支、分叉处以及动脉的内曲线处。然而,在房室管和直管中,血流是层流的,几乎检测不到初级纤毛。心腔内的初级纤毛通过抑制转化生长因子(TGF)信号传导来防止内皮细胞发生间充质转化和钙化。此外,血管内皮中的初级纤毛通过触发钙离子内流以及一氧化氮(NO)释放来保护内皮细胞免受紊乱剪切应力诱导的细胞损伤。而且,初级纤毛抑制动脉粥样硬化的进程。在本综述中,我们讨论了心血管系统中的纤毛发生、纤毛结构以及纤毛分布、功能和与剪切应力的协同信号转导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b31/7901939/3f5d4f700072/fphys-12-640774-g001.jpg

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