Modulation of oxidized-LDL receptor-1 (LOX1) contributes to the antiatherosclerosis effect of oleanolic acid

Jiang, Qixiao; Wang, Daoyan; Han, Yantao; Han, Ze‐Guang; Zhong, Weizhen; Wang, Chunbo

doi:10.1016/j.biocel.2015.10.023

Cited by 31 publications

(29 citation statements)

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“…On the other hand, OA was known for its antioxidant and anti‐inflammation effects (Tsai and Yin, ; Kong et al, ). In vivo studies also revealed that OA exerted anti‐atherosclerotic effects (Jiang et al, ); however, the role of OA in VSMC proliferation had yet to be investigated. In the current study, OA effectively alleviated ox‐LDL‐induced A7r5 cell proliferation, suggesting that the previously observed in vivo anti‐atherosclerotic effects are associated with this effect.…”

Section: Discussionmentioning

confidence: 99%

“…Oleanolic acid (OA) belongs to the pentacyclic triterpenoid family, which is found in various plants throughout the world (Ovesna et al, 2004;Sultana and Ata, 2008). OA has been reported to exert various benefits, including hypolipidemic, hepatoprotective, and anti-tumor effects (Kim et al, 2005;Jiang et al, 2015;Guo et al, 2017). In vitro studies had revealed its antioxidative and anti-inflammatory effects (Tsai and Yin, 2008;Jiang et al, 2015;Kong et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

Han

Jiang

Wang

et al. 2017

Cell Biology International

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Vascular smooth muscle cell (VSMC) proliferation is a major contributor to atherosclerosis. This study investigated the inhibitory effects of oleanolic acid (OA) against oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation in A7r5 cells and explored underlying molecular mechanism. The cell proliferation was quantified with cell counting kit-8 (CCK-8), in which ox-LDL significantly increased A7r5 cells proliferation, while OA pretreatment effectively alleviated such changes without inducing overt cytotoxicity, as indicated by lactate dehydrogenase (LDH) assay. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting revealed increased UCP2 and FGF-2 expression levels as well as decreased p53 and TSP-1 expression levels in A7r5 cells following ox-LDL exposure, while OA pretreatment reversed such changes. Furthermore, inhibiting UCP2 with genipin remarkably reversed the changes in the expression levels of FGF-2, p53, and TSP-1 induced by ox-LDL exposure; silencing FGF-2 with siRNA did not significantly change the expression levels of UCP2 but effectively reversed the changes in the expression levels of p53 and TSP-1, and activation of p53 with PRIMA-1 only significantly affected the changes in the expression levels of TSP-1, but not in UCP2 or FGF-2, suggesting a UCP-2/FGF-2/p53/TSP-1 signaling in A7r5 cells response to ox-LDL exposure. Additionally, co-treatment of OA and genipin exhibited similar effects to the expression levels of UCP2, FGF-2, p53, and TSP-1 as OA or genipin solo treatment in ox-LDL-exposed A7r5 cells, suggesting the involvement of UCP-2/FGF-2/p53/TSP-1 in the mechanism of OA. In conclusion, OA inhibits ox-LDL-induced VSMC proliferation in A7r5 cells, the mechanism involves the changes in UCP-2/FGF-2/p53/TSP-1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

Han

Jiang

Wang

et al. 2017

Cell Biology International

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“…Oxidation of LDL is one of the earliest events in the formation of atherosclerosis, and it has been shown that NADPH oxidase is critically involved in the process in both mice and humans by acting either directly or indirectly as a precursor of ROS which are utilized as substrates by other enzymes to generate more powerful oxidizing species [33, 34]. There are seven NADPH-dependent oxidoreductases (Nox enzymes) related isoforms, and four (Nox1, Nox2, Nox4, and Nox5) of them are expressed in vascular and immune cells [31, 35].…”

Section: Discussionmentioning

confidence: 99%

Knockout of Low Molecular Weight FGF2 Attenuates Atherosclerosis by Reducing Macrophage Infiltration and Oxidative Stress in Mice

Liang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fibroblast growth factor 2 (FGF2) plays a predominant role during angiogenesis in the adventitia and in atherosclerotic plaque. A dilemma exists, however, as to whether angiogenic stimulation by FGF2 for the prevention and treatment of atherogenesis is feasible. The aim of this study is to investigate the effect of the 18-kDa FGF-2 isoform on atherosclerosis progression in high-fat diet-fed apolipoprotein E knockout (ApoE-/-) mice. Methods: We established a model of atherosclerosis using ApoE and 18-kDa FGF-2 gene double knockout mice. They were randomly divided into three groups depending on the duration of diet: 8 weeks, 12 weeks and 16 weeks. Then, we studied the morphology and inflammatory factor staining in the atherosclerosis plaque of these mice. Results: Knockout of the 18-kDa FGF-2 isoform did not change the metabolic characteristics of the mice. Compared to the control group, knockout of the 18-kDa FGF-2 isoform significantly attenuated atherogenesis, reduced aortic plaques, reduced macrophage infiltration and suppressed oxidative stress in mice fed with a high fat diet at all-time points. Conclusions: 18-kDa FGF-2 aggravated the inflammatory reaction of atherosclerosis.

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“…3 Our previous work also demonstrated the critical role of the lectin-like ox-LDL receptor-1 in oxidized low density lipoprotein (ox-LDL)-induced oxidative stress and cytotoxicity as well as the protective effects of OA and its associated underlying mechanism of modulation on nicotinamide adenine dinucleotide phosphate oxidase. 7 However, nicotinamide adenine dinucleotide phosphate oxidase only accounts for part of ROS generation; another unignorable resource of ROS is mitochondria, which is also involved in lectin-like ox-LDL receptor-1-mediated marcophage activation. 8,9 This makes mitochondria a good target for further mechanism elucidation of OA.…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Effects of Oleanolic Acid in Human Umbilical Vascular Endothelial Cells is Mediated Via UCP2/ROS/Cytochrome C/AIF Pathway

Kong

Han

Wang³

et al. 2016

Journal of Cardiovascular Pharmacology

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The aim of this study is to assess the potential protective effect of oleanolic acid (OA) against ox-LDL induced damage in human umbilical vascular endothelial cells (HUVECs) and investigate potential mechanism of action including antioxidative effects and inhibition of mitochondria apoptosis pathway. Cell counting kit 8 was used to evaluate the viability of HUVECs. 2', 7'-DCFH-DA staining and flow cytometry was used to assess the levels of intracellular reactive oxygen species in HUVECs. The protein expression levels of uncoupling protein 2, cytochrome C, and apoptosis induction factors were measured by western blotting. The results indicated that OA treatment alleviated ox-LDL induced cytotoxicity in HUVECs and ameliorated the reactive oxygen species levels. Western blotting results demonstrated that OA treatment increased the expression level of uncoupling protein 2 and decreased the release of cytochrome C and apoptosis induction factors from mitochondria to cytoplasm, suggesting inhibition of mitochondria apoptosis pathway. In conclusion, OA could protect HUVECs from ox-LDL-induced cytotoxicity; its antioxidant property and inhibition of mitochondria apoptosis are likely crucial contributors.

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Modulation of oxidized-LDL receptor-1 (LOX1) contributes to the antiatherosclerosis effect of oleanolic acid

Cited by 31 publications

References 50 publications

The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

Knockout of Low Molecular Weight FGF2 Attenuates Atherosclerosis by Reducing Macrophage Infiltration and Oxidative Stress in Mice

Cytoprotective Effects of Oleanolic Acid in Human Umbilical Vascular Endothelial Cells is Mediated Via UCP2/ROS/Cytochrome C/AIF Pathway

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