Modulation of oxidized-LDL receptor-1 (LOX1) contributes to the antiatherosclerosis effect of oleanolic acid.
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 200μg/mL ox-LDL for 24h, 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.
Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
Qixiao
Q
Jiang
Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
Daoyan
D
Wang
Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
Yantao
Y
Han
The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, Shandong, China. Electronic address: zhiwu1218@126.com.
Zhiwu
Z
Han
Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
Weizhen
W
Zhong
Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China. Electronic address: cbwang666@126.com.
Chunbo
C
Wang
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D011784:Quail; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*
D008077:Lipoproteins, LDL; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495137:OLR1 protein, human; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D009828:Oleanolic Acid; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases
Antiatherosclerosis; LOX-1; Oleanolic acid; Oxidized low-density lipoprotein; Quails