Anisodamine Hydrobromide Protects Glycocalyx and Against the Lipopolysaccharide-Induced Increases in Microvascular Endot
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Cardiovascular Engineering and Technology ( 2020) https://doi.org/10.1007/s13239-020-00486-8
John Tarbell
Anisodamine Hydrobromide Protects Glycocalyx and Against the Lipopolysaccharide-Induced Increases in Microvascular Endothelial Layer Permeability and Nitric Oxide Production XIAOQIANG DU,1 HUAN LIU,1 YONGHUA YUE,2 QINGJIANG WU,2 WENLI JIANG,1 YAN QIU,1 and YE ZENG
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1
Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China; and 2Chengdu No. 1, Pharmaceutical Co., Ltd, Chengdu 610031, China (Received 11 May 2020; accepted 8 September 2020) Associate Editor Hanjoong Jo oversaw the review of this article.
Abstract Purpose—Anisodamine hydrobromide (Ani HBr) has been used to improve the microcirculation during cardiovascular disorders and sepsis. Glycocalyx plays an important role in preserving the endothelial cell (EC) barrier permeability and nitric oxide (NO) production. We aimed to test the hypothesis that Ani HBr could protect the EC against permeability and NO production via preventing glycocalyx shedding. Methods—A human cerebral microvascular EC hCMEC/D3 injury model induced by lipopolysaccharide (LPS) was established. Ani HBr was administrated to ECs with the LPS challenge. Cell viability was performed by Cell Counting Kit-8 assay. Cell proliferation and apoptosis were detected by EdU and Hoechst 33342 staining. Apoptosis and cell cycle were also assessed by flow cytometry with annexin V staining and propidium iodide staining, respectively. Then, adherens junction integrity was evaluated basing on the immunofluorescence staining of vascular endothelial cadherin (VEcadherin). The glycocalyx component heparan sulfate (HS) was stained in ECs. The cell permeability was evaluated by leakage of fluorescein isothiocyanate (FITC)-dextran. Cellular NO production was measured by the method of nitric acid reductase. Results—Ani HBr at 20 lg/mL significantly increased the viability of ECs with LPS challenge, but significantly inhibited the cell viability at 80 lg/mL, showing a bidirectional regulation of cell viability by Ani HBr. Ani HBr had not significantly change the LPS-induced EC proliferation. Ani HBr significantly reversed the induction of LPS on EC apoptosis. Ani HBr reinstated the LPS-induced glycocalyx and VE-cadherin shedding and adherens junction disruption.
Address correspondence to Ye Zeng, Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic mail: [email protected]
Ani HBr significantly alleviated LPS-induced EC layer permeability and NO production. Conclusion—Ani HBr protects ECs against LPS-induced increase in cell barrier permeability and nitric oxide production via preserving the integrity of glycocalyx. Ani HBr is a promising drug to rescue or protect the glycocalyx. Keywords—Glycocalyx, Lipopolysaccharide.
Endothelial
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Anisodamine,
INTRODUCTION Cardiovascular diseases and sepsis are closely associated wi
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