期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 8, 期 21, 页码 -出版社
AME PUBL CO
DOI: 10.21037/atm-20-3426
关键词
Atherosclerosis; endothelial cells; shear stress; focal adhesion; endothelial barrier dysfunction
资金
- National Natural Science Funds of China [30871047]
- Funds of Guangdong Provincial Project of Science and Technology [2013B021800294]
Background: Endothelial cells play a pivotal role in cardiovascular physiology and pathology by providing a barrier to the bloodstream. In the current study, we investigated the phenotype and barrier function of endothelial cells in response to shear stress under pro-atherogenic conditions. Methods: Endothelial cells were exposed to laminar shear stress (LSS) in a parallel-plate flow chamber containing oxidized low-density lipoprotein (oxLDL) in the perfusion solution, or remained static. We quantified the response of endothelial monolayers to LSS and oxLDL in terms of cell viability, barrier integrity, vascular endothelial cadherin (VE-cadherin) availability, focal adhesion (FA) remodeling, and monocyte-endothelial interactions. Results: Our results showed that oxLDL stimulation and static conditions synergized to enhance endothelial barrier disruption. Under the same oxLDL challenge, the application of 25 dynes/cm(2) LSS on the endothelial monolayer decreased the passage of fluorescein isothiocyanate (FITC)-dextran by 37.79%, increased transendothelial electrical resistance (TEER) by 24.97% compared with static cells (P<0.05), which was accompanied by reduced intercellular gap formation, relatively solid cell-substrate adhesion. Compared with static cells, endothelial cells exposed to both laminar flow and oxLDL had less small FAs, less monocyte adhesion and transmigration, and alleviated overexpression of VCAM-1 and MCP-1. Meanwhile, the oxLDL-induced internalization of VE-cadherin and vinculin were also attenuated by laminar flow, and this change was more pronounced at LSS of 25 dynes/cm(2) than 5 dynes/cm(2). Conclusions: Static conditions favor, whereas physiologically higher levels of LSS ameliorate endothelial barrier disruption under pro-atherogenic stress, which is related to the improved availability of VE-cadherin and vinculin on the cell surface.
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