Modulation of oxidized-LDL receptor-1 (LOX1) contributes to the antiatherosclerosis effect of oleanolic acid |
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| Affiliation: | 1. Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China;2. The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, Shandong, China;1. Department of Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark;2. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark;1. TransTissue Technologies GmbH, Berlin, Germany;2. Department of Rheumatology, Laboratory for Tissue Engineering, Charité – Universitätsmedizin Berlin, Berlin, Germany;3. Department of Orthopedics, Experimental Rheumatology Unit, Friedrich Schiller University, Jena, Germany;1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Sciences Centre, Manchester M13 9WL, UK;2. Maternal and Fetal Health Research Centre, St Mary''s Hospital, Central Manchester University Hospitals NHS Foundation Trust, UK;3. Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK;4. Gravida, University of Auckland, Auckland, New Zealand;1. Department of Biology, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5;2. Department of Pediatrics and the Graduate Program in Medical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5;3. Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5;4. Chronic Disease Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1Y 4E9;5. Department of Biomedical and Molecular Sciences, Queens University, Kingston, Ontario, Canada K7L 3N6;6. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6;1. Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, College of Life Science, South China Normal University, Guangzhou, 510631, PR China;2. State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, PR China |
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| Abstract: | Oleanolic acid (OA) is a bioactive pentacyclic triterpenoid. The current work studied the effects and possible mechanisms of OA in atherosclerosis. Quails (Coturnix coturnix) were treated with high fat diet with or without OA. Atherosclerosis was assessed by examining lipid profile, antioxidant status and histology in serum and aorta. Human umbilical vein endothelial cells (HUVECs) were exposed to 200 μg/mL ox-LDL for 24 h, then cell viability was assessed with MTT assay; reactive oxygen species (ROS) was assessed with DCFDA staining. Expression levels of LOX-1, NADPH oxidase subunits, nrf2 and ho-1 were measured with real time PCR and western blotting. Furthermore, LOX-1 was silenced with lentivirus and the expression levels assessment was repeated. OA treatment improved the lipid profile and antioxidant status in quails fed with high fat diet. Histology showed decreased atherosclerosis in OA treated animals. Ox-LDL exposure decreased viability and induced ROS generation in HUVECs, and this progression was alleviated by OA pretreatment. Moreover, elevated expression of LOX-1, NADPH oxidase subunits, nrf2 and ho-1 were observed in ox-LDL exposed HUVECs. OA pretreatment prevented ox-LDL induced increase of LOX-1 and NADPH oxidase subunits expression, while further increased nrf2 and ho-1 expression. Silencing of LOX-1 abolished ox-LDL induced effects in cell viability, ROS generation and gene expression. OA could alleviate high fat diet induced atherosclerosis in quail and ox-LDL induced cytotoxicity in HUVECs; the potential mechanism involves modulation of LOX-1 activity, including inhibition of expression of NADPH oxidase subunits and increase of the expression of nrf2 and ho-1. |
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| Keywords: | Oleanolic acid Quails Antiatherosclerosis Oxidized low-density lipoprotein LOX-1 |
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