Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model

Hinagata, Jun-ichi; Kakutani, Makoto; Fujii, Tomoyuki; Naruko, Takahiko; Inoue, N.; Fujita, Yoshiko; Mehta, Jawahar L.; Ueda, Makiko; Sawamura, Tatsuya

doi:10.1016/j.cardiores.2005.08.013

Cited by 70 publications

(44 citation statements)

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“…There is also a risk of bias due to the healthy worker effect 24) . Both in vitro and animal experiments have shown that the LAB is related to endothelial dysfunction, which leads to lipid sedimentation 3,4) , inflammation 25) , migration and the proliferation of smooth muscle 26) , and to the formation of foam cells 27) . All of sex.…”

Section: Discussionmentioning

confidence: 99%

“…CRP is a marker for inflammation that is clinically useful in the evaluation of potential atherosclerosis, because inflammation enhances endothelial dysfunction. LAB is also involved in promoting inflammation 25) , but it influences various other reactions leading to the progression of atherosclerosis 3,4,26,27) . The positive relationship between the LAB and the CAVI in men in the present study was not influenced by adding the hs-CRP level to regression models; therefore, this result may indicate that the LAB has an influence on the development of atherosclerosis caused not only by inflammation, but also by other pathways.…”

Section: Discussionmentioning

confidence: 99%

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The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in Healthy Community Inhabitants: The KOBE Study

Sugiyama

Higashiyama

Wakabayashi

et al. 2015

JAT

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in Healthy Community Inhabitants: The KOBE Study

Sugiyama

Higashiyama

Wakabayashi

et al. 2015

JAT

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“…LOX-1 has been reported to induce apoptosis of endothelial cells, which is associated with the atherosclerosis and restenosis of artery. 7,19 Because the endothelium has the ability to improve arterial injury, the denudation of the endothelium by coronary intervention may, thus, accelerate the occurrence of restenosis. Drug-eluting stents (DESs) have been shown to be effective for preventing in-stent restenosis.…”

Section: Discussionmentioning

confidence: 99%

“…6 The LOX-1 expression has been reported to significantly increase in the neointima after balloon injury in various animal models of neointimal hyperplasia, such as rats and rabbits. Hinagata et al 7 reported neointimal hyperplasia after balloon injury to be markedly attenuated by treatment with anti-LOX-1 antibody in a rat model. These findings suggest that LOX-1 expressed in the neointima is involved in the pathogenesis of restenosis after arterial injury, and, therefore, LOX-1 may be a potential therapeutic target for the prevention/treatment of neointimal hyperplasia and restenosis after arterial injury.…”

mentioning

confidence: 99%

Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Attenuates Restenosis of the Artery After Injury

Yao

Fukuda²,

Ueno³

et al. 2008

Hypertension

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Abstract-Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can support the binding, internalization, and proteolytic degradation of oxidized low-density lipoprotein. The LOX-1 expression increases in the neointima after balloon injury. To develop an efficient compound to inhibit LOX-1, we designed and synthesized a novel gene silencer pyrrole-imidazole (PI) polyamide targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) to the activator protein-1 binding site. We examined the effects of PI polyamide to LOX-1 on the LOX-1 promoter activity, the expression of LOX-1 mRNA and protein, and neointimal hyperplasia of the rat carotid artery after balloon injury. PI polyamide to LOX-1 significantly inhibited the rat LOX-1 promoter activity and decreased the expression of LOX-1 mRNA and protein. After balloon injury of the arteries, PI polyamide to LOX-1 was incubated for 10 minutes. Fluorescein isothiocyanate-labeled PI polyamide was distributed to almost all of the nuclei in the injured artery. PI polyamide to LOX-1 (100 g) significantly inhibited the neointimal thickening by 58%. PI polyamide preserved the re-endothelialization in the injured artery. PI polyamide significantly inhibited the expression of LOX-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9 mRNAs in the injured artery. The synthetic PI polyamide to LOX-1 decreased the expression of LOX-1 and inhibited neointimal hyperplasia after arterial injury. This novel gene silencer PI polyamide to LOX-1 is, therefore, considered to be a feasible agent for the treatment of in-stent restenosis. Key Words: basic science Ⅲ endothelium Ⅲ gene therapy Ⅲ cytokines Ⅲ polyamide Ⅲ LOX-1 Ⅲ restenosis C oronary artery restenosis after angioplasty occurs in Ϸ30% of all patients. 1,2 Despite the widespread use of intracoronary stents, in-stent restenosis remains a major clinical problem, occurring in Յ50% of high-risk patients. 3 The development of neointimal hyperplasia after arterial injury contributes to the pathogenesis of restenosis. Several factors are involved in the initiation and progression of neointimal hyperplasia. Coronary arterial diseases are known to be associated with several risks, such as dyslipidemia, hypertension, smoking, and diabetes. A pivotal common factor in these risks is oxidative stress, which also induces restenosis of the coronary artery. 4 The oxidized low-density lipoprotein (ox-LDL) is recognized to be a major cause of endothelial dysfunction in atherogenesis. 5 Lectin-like ox-LDL receptor-1 (LOX-1), a receptor for ox-LDL, is a membrane protein that is expressed in both the vascular endothelium and vascular-rich organs. LOX-1 can support the binding, internalization, and proteolytic degradation of ox-LDL. 6 The LOX-1 expression has been reported to significantly increase in the neointima after balloon injury in various animal models of neointimal hyperplasia, such as rats and rabbits. Hinagata et al 7 reported neointimal hyperplasia after ba...

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“…The reactive intimal thickening, ROS generation and leukocyte infiltration were attenuated by the administration of anti-LOX-1 antibody. 33 Gene silencer pyrrole-imidazole (PI) polyamide targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) inhibits neointima thickening and preserves the re-endothelialization after balloon injury. 34 Thus, LOX-1 is involved in multiple phases of vascular dysfunction, including endothelial dysfunction, atherogenesis and restenosis.…”

Section: Lox-1 and The Vascular Systemmentioning

confidence: 99%

LOX-1 The Multifunctional Receptor Underlying Cardiovascular Dysfunction

Ogura

Kakino

Sato

et al. 2009

Circ J

102

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Oxidatively modified low-density lipoprotein (oxLDL) is implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is the initial change in the vascular wall that induces morphological changes for atheroma-formation. Lectin-like oxidized LDL receptor-1 (LOX-1) was identified as the receptor for oxLDL that was thought to be a major cause of endothelial dysfunction. LOX-1 has been demonstrated to contribute not only to endothelial dysfunction, but also to atherosclerotic-plaque formation, myocardial infarction and intimal thickening after balloon injury. Recent findings on the genetics of LOX-1 and the methodology to detect it and its ligands would further facilitate the examination of the receptor's pathophysiological contribution in atherosclerosis.

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Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model

Abstract: The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty.

Cited by 70 publications

References 50 publications

The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in Healthy Community Inhabitants: The KOBE Study

The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in Healthy Community Inhabitants: The KOBE Study

Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Attenuates Restenosis of the Artery After Injury

LOX-1 The Multifunctional Receptor Underlying Cardiovascular Dysfunction

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