Effect of endothelial cell proliferation on atherogenesis: A role of p21// in monocyte adhesion to endothelial cells

Obikane, Hiyo; Abiko, Yoshimitsu; Ueno, Hikaru; Kusumi, Yoshiaki; Esumi, Mariko; Mitsumata, Masako

doi:10.1016/j.atherosclerosis.2010.05.029

Cited by 35 publications

(28 citation statements)

References 30 publications

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“…In addition, the function of p21/CIP-1 has been demonstrated to up-regulate the cellular anti-oxidant response via direct binding to the master HO-1 gene transcriptional regulator Nrf2 (Chen et al, 2009). These findings are in keeping with a recent report showing a major regulatory role for p21/CIP-1 in endothelial cell proliferation in atherosclerosis (Obikane et al, 2010), and may suggest that the interplay of p21/CIP-1 with HO-1 and/or Nrf2 is involved in the pathogenesis of TV.…”

Section: Pharmacological Regulation Of Ho-1 and Its Effector Moleculesupporting

confidence: 92%

Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

Lundvig¹,

Immenschuh²,

Wagener³

2012

Front. Pharmacol.

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Upon injury, prolonged inflammation and oxidative stress may cause pathological wound healing and fibrosis, leading to formation of excessive scar tissue. Fibrogenesis can occur in most organs and tissues and may ultimately lead to organ dysfunction and failure. The underlying mechanisms of pathological wound healing still remain unclear, and are considered to be multifactorial, but so far, no efficient anti-fibrotic therapies exist. Extra- and intracellular levels of free heme may be increased in a variety of pathological conditions due to release from hemoproteins. Free heme possesses pro-inflammatory and oxidative properties, and may act as a danger signal. Effects of free heme may be counteracted by heme-binding proteins or by heme degradation. Heme is degraded by heme oxygenase (HO) that exists as two isoforms: inducible HO-1 and constitutively expressed HO-2. HO generates the effector molecules biliverdin/bilirubin, carbon monoxide, and free iron/ferritin. HO deficiency in mouse and man leads to exaggerated inflammation following mild insults, and accumulating epidemiological and preclinical studies support the widely recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory effects of the activity of the HO system and its effector molecules. In this review, we address the potential effects of targeted HO-1 induction or administration of HO-effector molecules as therapeutic targets in fibrotic conditions to counteract inflammatory and oxidative insults. This is exemplified by various clinically relevant conditions, such as hypertrophic scarring, chronic inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in transplantation.

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Section: Pharmacological Regulation Of Ho-1 and Its Effector Moleculesupporting

confidence: 92%

Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

Lundvig¹,

Immenschuh²,

Wagener³

2012

Front. Pharmacol.

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“…First, TXNIP expression in EC is low but highly induced in EC exposed to disturbed flow, inflammatory cytokines, and hyperglycemia. [41][42][43] Second, TXNIP binding to TRX1 relieves inhibition of ASK1 enabling c-Jun N-terminal kinase-dependent induction of vascular cell adhesion molecule-1. 13 In addition, previous studies that used a high concentration of ROS indicated TXNIP was proapoptotic via activation of multiple death pathways.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin-Interacting Protein Mediates TRX1 Translocation to the Plasma Membrane in Response to Tumor Necrosis Factor-α

Spindel¹,

Berk²

2011

ATVB

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Objective-Thioredoxin-interacting protein (TXNIP) promotes inflammation in endothelial cells (EC) by binding to thioredoxin-1 (TRX1) in a redox-dependent manner. Formation of the TXNIP-TRX1 complex relieves inhibition of the apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase-vascular cell adhesion molecule-1 pathway. Because TXNIP is an ␣-arrestin with numerous protein-protein interacting domains, we hypothesized that TXNIP-TRX1 trafficking should alter function of EC exposed to reactive oxygen species (ROS). Methods and Results-In response to physiological levels of ROS (10 ng/mL tumor necrosis factor-␣ and 30 mol/L H 2 O 2 ), TXNIP-TRX1 translocated to the plasma membrane in human umbilical vein EC, with a peak at 30 minutes, as measured by immunofluorescence colocalization with vascular endothelial-cadherin, cell fractionation, and membrane sheet assay. TXNIP-mediated translocation of TRX1 to the membrane required TXNIP and TRX1 binding, as evidenced by inability of the ROS-insensitive TXNIP-Cys247Ser mutant to promote membrane localization. Vascular endothelial growth factor signaling required TXNIP, as shown by significant decreases in plasma membrane tyrosine phosphorylation and EC migration after TRX1 knockdown. Furthermore, TXNIP knockdown increased human umbilical vein EC apoptosis induced by tumor necrosis factor. Rescue with TXNIP-wild-type but not TXNIP-Cys247Ser prevented cell death. Key Words: apoptosis Ⅲ vascular endothelial growth factor receptor-2 Ⅲ redox Ⅲ thioredoxin Ⅲ thioredoxin-interacting protein T hioredoxin-1 (TRX1), a highly conserved and ubiquitous oxidoreductase, is responsible for restoring oxidized proteins to their reduced form. 1 In addition to its role as a scavenger of reactive oxygen species (ROS), TRX1 regulates transcription and cell signaling, resulting in the modulation of cell growth and survival. 2 To this end, TRX1 exerts a protective effect by controlling signal transduction via the regulation of kinase and phosphatase action. [3][4][5] The activity of TRX1 is regulated by TRX1-interacting protein (TXNIP), which exhibits homology with ␤-arrestin proteins. 6,7 This interaction requires cysteine 247 of TXNIP and involves the formation of a mixed disulfide with reduced TRX1. 8 The nuclear accumulation of TRX1 in cardiomyocytes was recently shown to protect against cardiac hypertrophy and was found to require the action of TXNIP as a scaffold. 9 In addition, changes in the localization of TRX1 have been shown necessary for the activation of the prosurvival kinase Akt in response to ischemic preconditioning of the heart. 10 Inflammation induced by cytokines, such as tumor necrosis factor ␣ (TNF-␣), requires the ROS-mediated dissociation of TRX1 from apoptosis signal-regulating kinase 1 (ASK1). 11 The release of TRX1 from ASK1 mediates ASK1 activation and endothelial cell (EC) apoptosis in response to TNF-␣. 12 In addition, overexpression of TXNIP was shown to disrupt TRX1-ASK1 binding and mediate an increase in prooxidant cell death. 7 It is important to note that...

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“…Various pathological events, including proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), formation of foam cells, deposition of extracellular lipid, persistent inflammation and oxidative stress, contribute to the progression of atherosclerosis (1–3). Atherosclerosis has been reported to be the primary cause of myocardial infarction, heart failure, myocardial ischemia as well as stroke and accounts for high mortality and morbidity worldwide (4,5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA let-7g alleviates atherosclerosis via the targeting of LOX-1 in vitro and in vivo

Liu

Gao

Liu

et al. 2017

International Journal of Molecular Medicine

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Atherosclerosis is a chronic arterial disease and the leading cause of stroke and myocardial infarction. Micro RNAs (miRNAs or miRs) have been reported to act as essential modulators during the progression of atherosclerosis. Although miR-let-7g has been demonstrated to contribute to maintaining endothelial function and vascular homeostasis, it is not known whether miR-let-7g exerts a therapeutic effect on experimental atherosclerosis. The aim of this study was to investigate the effects of miR-let-7g on atherosclerosis in vivo and in vitro and to explore its underlying mechanisms. Data from our study showed that exogenous lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 or OLR1) overexpression resulted in the significant promotion of proliferation and migration of human aortic smooth muscle cells (ASMCs), whereas such changes induced by LOX-1 were obviously suppressed by transfection of miR-let-7g. We later confirmed that LOX-1 is a potential target of miR-let-7g, and miR-let-7g markedly inhibited LOX-1 expression in ASMCs by directly binding to the 3′ untranslated region of LOX-1. Furthermore, in a hyperlipidemic apolipoprotein E knockout (ApoE−/−) mouse model, intravenous delivery of miR-let-7g mimics obviously attenuated high-fat diet-induced neointima formation and atherosclerotic lesions, accompanied by the significant downregulation of LOX-1, which was consistent with the effect of miR-let-7g on ASMCs. Taken together, our data revealed that miR-let-7g exhibits anti-atherosclerotic activity, at least partially by targeting the LOX-1 signaling pathway. This study suggests that miR-let-7g may be a therapeutic candidate for treating atherosclerosis, and provides novel insight into miRNA-based therapy for this disease.

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Effect of endothelial cell proliferation on atherogenesis: A role of p21// in monocyte adhesion to endothelial cells

Cited by 35 publications

References 30 publications

Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

Thioredoxin-Interacting Protein Mediates TRX1 Translocation to the Plasma Membrane in Response to Tumor Necrosis Factor-α

MicroRNA let-7g alleviates atherosclerosis via the targeting of LOX-1 in vitro and in vivo

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