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  • 1 Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China
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Abstract

Although the use of aspirin has substantially reduced the risks of cardiovascular events and death, its potential mechanisms have not been fully elucidated. In a previous study, we found that aspirin triggers cellular autophagy. In the present study, we aimed to determine the protective effects of aspirin on human coronary artery endothelial cells (HCAECs) and explore its underlying mechanisms. HCAECs were treated with oxidized low-density lipoprotein (ox-LDL), angiotensin II (Ang-II), or high glucose (HG) with or without aspirin stimulation. The expression levels of endothelial nitric oxide (NO) synthase (eNOS), p-eNOS, LC3, p62, phosphor-nuclear factor kappa B (p-NF-κB), p-p38 mitogen-activated protein kinase (p-p38 MAPK), and Beclin-1 were detected via immunoblotting analysis. Concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured via ELISA. NO levels were determined using the Griess reagent. Autophagic flux was tracked by tandem mRFP-GFP-tagged LC3. Results showed that aspirin increased eNOS level and reduced injury to the endothelial cells (ECs) caused by ox-LDL, Ang-II, and HG treatment in a dose-dependent manner. Aspirin also increased the LC3II/LC3I ratio, decreased p62 expression, and enhanced autophagic flux (autophagosome and autolysosome puncta) in the HCAECs. p-NF-κB and p-p38 mitogen-activated protein kinase inhibition, sVCAM-1 and sICAM-1 secretion, and eNOS activity promotion by aspirin treatment were found to be dependent on Beclin-1. These results suggested that aspirin can protect ECs from ox-LDL-, Ang-II-, and HG-induced injury by activating autophagy in a Beclin-1-dependent manner.

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