The protective effects of azilsartan against oscillatory shear stress‐induced endothelial dysfunction and inflammation are mediated by KLF6. Issue 6 (1st April 2021)

• Record Type: Journal Article
• Authors: Wei, Guoqian; Zhu, Dayong; Sun, Yongtao; Zhang, Lan; Liu, Xian; Li, Ming; Gu, Jinxia
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 6(2021)
• Page Start: 1
• Page End: 8
• Publication Date: 2021-04-01
• Subjects: atherosclerosis -- azilsartan -- endothelial dysfunction -- KLF6 -- oscillatory shear stress -- oxidative stress; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22766
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: Background and Purpose: Atherosclerosis is a common cardiovascular disease with high morbidity and mortality. It is reported to be related to oscillatory shear stress (OSS)‐induced endothelial dysfunction and excessive production of inflammatory factors. Azilsartan, a specific antagonist of the angiotensin II receptor, has been approved for the management of hypertensive subjects with diabetes mellitus type II (DMII). The present study will investigate the effects of azilsartan against OSS‐induced endothelial dysfunction and inflammation, as well as the underlying mechanism. Materials and Methods: Cell viability was detected using an MTT (3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide) assay. Quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and enzyme‐linked immunosorbent assay were used to determine the expression levels of IL‐6, TNF‐α, IL‐1β, VCAM‐1, and ICAM‐1 in human aortic endothelial cells (HAECs). Generation of reactive oxygen species (ROS) was measured using 2ʹ‐7ʹdichlorofluorescin diacetate (DCFH‐DA) staining, and the level of reduced glutathione (GSH) was evaluated using a commercial kit. The adhesion of THP‐1 monocytes to HAECs was evaluated using calcein‐AM staining. The expression level of KLF6 was determined using qRT‐PCR and Western blot analysis. Results: According to the result of the MTT assay, 5 and 10 μM azilsartan were considered as the optimized concentrations applied in the present study. The elevated production of IL‐6, TNF‐α, and IL‐1β, increased levels of ROS, decreased levels of reduced GSH, upregulated VCAM‐1, ICAM‐1, and E‐selectin, and the aggravated adhesion of THP‐1 cells to HAECs induced by OSS were all reversed by the introduction of azilsartan. The downregulation of KLF6 induced by OSS was significantly reversed by azilsartan. By knocking down the expression of KLF6, the suppressed adhesion of THP‐1 cells to the HAECs, and the downregulation of VCAM‐1 and ICAM‐1 induced by azilsartan in OSS‐stimulated HAECs were greatly reversed. Conclusion: The protective effects of azilsartan against OSS‐induced endothelial dysfunction and inflammation might be mediated by KLF6.