Oxidized High-Density Lipoprotein Induces the Proliferation and Migration of Vascular Smooth Muscle Cells by Promoting the Production of ROS

Wang, Yan; Ji, Liang; Jiang, Rengui; Zheng, Lemin; Liu, Donghui

doi:10.5551/jat.19448

Cited by 38 publications

(28 citation statements)

References 44 publications

(67 reference statements)

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“…It is well known that oxidative stress-induced proliferation of VSMCs plays a critical role in pathogenesis of atherosclerosis [26–28], and a mount of molecules were demonstrated to inhibit HASMCs proliferation mainly via attenuating oxidative stress [5, 7, 29–32]. Here, we found that ISL could effectively lowered ROS level in HASMCs and this may attribute to the increased SOD activity.…”

Section: Discussionsupporting

confidence: 54%

The inhibitory effect of Isoliquiritigenin on the proliferation of human arterial smooth muscle cell

Chen

Deng

Lin

2017

BMC Pharmacol Toxicol

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BackgroundIsoliquiritigenin (ISL) has various biological activities including as antioxidant and an inhibitor of PI3K/AKT signaling pathway. However, both oxidative stress and activated PI3K/AKT signaling contribute to the aberrant proliferation of vascular smooth muscle cells (VSMCs). This study is aimed to explore the effect of ISL on the proliferation of human arterial smooth muscle cells (HASMCs) and to investigate the underlying mechanisms.MethodsBrdU incorporation, cell cycle and reactive oxygen species (ROS) in normal or ISL treated HASMCs were analyzed by flow cytometry. Cell viablity was measured by CCK-8. Protein expression levels were examined by Western blot, and superoxide dismutase (SOD) activity was detected by using commercial kit.ResultsWe observed that ISL could inhibit the proliferation of HASMCs in a dose and time dependent manner. Cell cycle of ISL treated HASMCs arrested mainly in G1/S phase and accompanied with elevated expression of p27 and decreased expression of CyclinD1 and CyclinE. In addition, ISL could down-regulated the expression of p-PI3K and p-AKT, alleviated oxidative stress and enhanced the SOD activity in HASMCs. Furthermore, H2O2 treatment partly improved cell viability and up regulated p-PI3K and p-AKT in HASMCs.ConclusionsTherefore, we concluded that ISL inhibited the proliferation of HASMCs via attenuating oxidative stress and suppressing PI3K/AKT signaling pathway. The inhibitory effect of ISL on PI3K/AKT signaling pathway, at least partly, was mediated by ROS.

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Section: Discussionsupporting

confidence: 54%

The inhibitory effect of Isoliquiritigenin on the proliferation of human arterial smooth muscle cell

Chen

Deng

Lin

2017

BMC Pharmacol Toxicol

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“…Moreover, ox-HDL induces ROS production and NF-B activation and increases the expression of several proinflammatory genes, including tumor necrosis factor- and cyclooxygenase-2 in endothelial cells and macrophages, which accelerate atherosclerosis development (10,40,41). Furthermore, ox-HDL can induce the proliferation and migration of vascular smooth muscle cells by promoting ROS production (8). In this study, we found apoptosis, oxidative stress, and upregulation of GRP78 and CHOP.…”

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediamentioning

confidence: 66%

“…After transfection for 48 h, the cells were treated with ox-HDL (100 mg/L) for 24 h. The silencing of TLR4 and CHOP were validated by Western blot. The TLR4 siRNAs are 5′-GCCUAAACCCAGUCUGUUUdTdT-3′ (sense) and 5′-AAACAGACUGGGUUUAGG CdTdT-3′ (antisense), and the (ox-HDL) loses the antiatherogenic functions of native HDL (5-7) and exerts effects instead by inducing proliferation and migration of vascular smooth muscle cells (8), promoting platelet activation (9), and causing apoptosis in endothelial cells (10). Ox-HDL has been detected in atherosclerotic plaques (11).…”

Section: Cell Culture and Sirna Transfectionmentioning

confidence: 99%

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Yao¹,

Tian²,

Zhao³

et al. 2017

Journal of Lipid Research

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This article is available online at http://www.jlr.org Atherosclerosis, one of the prime causes of heart attack and stroke, has been well known as a lipid-driven inflammatory disease characterized by macrophage accumulation in subendothelial space. Apoptosis of macrophage-derived foam cells, especially in advanced atherosclerotic lesions where phagocytic clearance of dead and dying cells is defective, results in acellular necrotic lesions that are prone to plaque rupture and thrombosis formation, leading to the majority of acute vascular events (1). Thus, deeper understanding of the mechanisms of macrophage apoptosis may pave the way for developing novel therapeutic strategies to effectively prevent atherosclerotic plaque rupture and subsequent clinical complications (2). Oxidized LDL (ox-LDL) has been recognized as a major inducer, promoting foam cell formation and apoptosis in macrophages (3). In contrast, HDL exerts antiatherogenic functions such as promoting reverse cholesterol transport, suppressing inflammation, inhibiting LDL oxidation, and increasing endothelial nitric oxide production (4). However, accumulating evidence suggests that HDL, like LDL, is also susceptible to oxidative modification. Oxidized HDL Abstract Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.

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“…Previous studies have revealed that oxidative modification of HDL impairs its antiatherogenic abilities from many aspects such as attenuating paraoxonase activity and inhibiting reverse cholesterol transport . Furthermore, oxidized HDL may become pro‐atherogenic by promoting ROS production, increasing proinflammatory factor expression, inducing the proliferation and migration of vascular smooth muscle cells, and causing apoptosis in endothelial cells and macrophages . In addition to oxidative modification, HDL can also be glycated in diabetes and the biological properties of HDL are altered including the reduced paraoxonase activity and anti‐inflammatory function, and the decreased capacity to mediate reverse cholesterol transport .…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress‐dependent autophagy inhibits glycated high‐density lipoprotein‐induced macrophage apoptosis by inhibiting CHOP pathway

Tian

Panpan

et al. 2019

J Cellular Molecular Medi

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This study was designed to explore the inductive effect of glycated high‐density lipoprotein (gly‐ HDL ) on endoplasmic reticulum ( ER ) stress‐C/ EBP homologous protein ( CHOP )‐mediated macrophage apoptosis and its relationship with autophagy. Our results showed that gly‐ HDL caused macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase‐like ER kinase ( PERK ) and eukaryotic translation initiation factor 2α, and CHOP up‐regulation, which were inhibited by 4‐phenylbutyric acid ( PBA , an ER stress inhibitor) and the gene silencing of PERK and CHOP . Similar data were obtained from macrophages treated by HDL isolated from diabetic patients. Gly‐ HDL induced macrophage autophagy as assessed by up‐regulation of beclin‐1, autophagy‐related gene 5 and microtubule‐associated protein one light chain 3‐ II , which were depressed by PBA and PERK si RNA . Gly‐ HDL ‐induced apoptosis, PERK phosphorylation and CHOP up‐regulation were suppressed by rapamycin (an autophagy inducer), whereas aggravated by 3‐methyladenine (an autophagy inhibitor) and beclin‐1 si RNA . Administration of diabetic apoE −/− mice with rapamycin attenuated MOMA ‐2 and CHOP up‐regulation and apoptosis in atherosclerotic lesions. These data indicate that gly‐ HDL may induce macrophage apoptosis through activating ER stress‐ CHOP pathway and ER stress mediates gly‐ HDL ‐induced autophagy, which in turn protects macrophages against apoptosis by alleviating CHOP pathway.

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Oxidized High-Density Lipoprotein Induces the Proliferation and Migration of Vascular Smooth Muscle Cells by Promoting the Production of ROS

Cited by 38 publications

References 44 publications

The inhibitory effect of Isoliquiritigenin on the proliferation of human arterial smooth muscle cell

The inhibitory effect of Isoliquiritigenin on the proliferation of human arterial smooth muscle cell

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Endoplasmic reticulum stress‐dependent autophagy inhibits glycated high‐density lipoprotein‐induced macrophage apoptosis by inhibiting CHOP pathway

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