In Vivo Low-Density Lipoprotein Exposure Induces Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Correlated With Activator Protein-1 Expression

Verna, Lynne; Ganda, Chintya; Stemerman, Michael B.

doi:10.1161/01.atv.0000222152.83069.3f

Cited by 31 publications

(28 citation statements)

References 36 publications

(31 reference statements)

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“…101 In vivo administration of native LDL into Ldlr Ϫ/Ϫ -recipient mice induces ICAM-1 as well as VCAM-1 expression. 102 In agreement with in vitro studies, immunohistochemical studies of human vessels indicate that human atherosclerotic plaques contain SMCs that express ICAM-1 in response to IL-1␤. 81 Pretreatment of Apoe Ϫ/Ϫ mice with Abs against ICAM-1 reduced short-term M⌽ homing into atherosclerotic lesions byϷ70%.…”

Section: Icam-1 and ␤ 2 Integrinssupporting

confidence: 70%

Vascular Adhesion Molecules in Atherosclerosis

Galkina

Ley

2007

ATVB

679

513

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Abstract-Numerous reports document the role of vascular adhesion molecules in the development and progression of atherosclerosis. Recent novel findings in the field of adhesion molecules require an updated summary of current research. In this review, we highlight the role of vascular adhesion molecules including selectins, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule1 (ICAM-1), PECAM-1, JAMs, and connexins in atherosclerosis. The immune system is important in atherosclerosis, and significant efforts are under way to understand the vascular adhesion molecule-dependent mechanisms of immune cell trafficking into healthy and atherosclerosis-prone arterial walls. This review focuses on the role of vascular adhesion molecules in the regulation of immune cell homing during atherosclerosis and discusses future directions that will lead to better understanding of this disease. (Arterioscler

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Section: Icam-1 and ␤ 2 Integrinssupporting

confidence: 70%

Vascular Adhesion Molecules in Atherosclerosis

Galkina

Ley

2007

ATVB

679

513

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“…While Statin mediated reduction of VCAM-1 expression is considered to be dependent on the eNOS pathway 43 , this is the first report showing that Ezetimibe is capable of reducing vascular VCAM-1 expression independent of eNOS function. This effect may be related to the reduction of plasma LDL cholesterol in our study, as Verna et al report that LDL can directly induce endothelial adhesion molecule expression by activation of the AP-1 regulatory pathway 44 . Consistent with the Ezetimibe mediated reduction of endothelial activation, mononuclear cell infiltration of the aorta was significantly reduced in apoE ko mice and apoE/eNOS dko mice.…”

Section: Discussionsupporting

confidence: 56%

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

Kuhlencordt¹,

Padmapriya²,

Rützel³

et al. 2009

Atherosclerosis

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Objective-Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS.Methods/Results-ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group.Conclusion-Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway.

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“…31,36,37 Because these transcription factors have been involved in the regulation of inducible chemokines including CCL20, 34,35 as a first approach we showed that inhibitors of NF-B signaling prevented the upregulation of CCL20 mRNA levels. The involvement of a NF-B site located in the proximal region of CCL20 promoter was demonstrated by serial deletion analysis of promoter-luciferase constructs, site-directed mutagenesis, EMSA, and chromatin immunoprecipitation assays.…”

Section: Discussionmentioning

confidence: 96%

CCL20 Is Increased in Hypercholesterolemic Subjects and Is Upregulated By LDL in Vascular Smooth Muscle Cells

Calvayrac

Rodríguez-Calvo

Alonso

et al. 2011

ATVB

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Objective-Our aim was to analyze the regulation of CC Chemokine ligand 20 (CCL20) by LDL in human vascular smooth muscle cells (VSMC). Methods and Results-In asymptomatic subjects, circulating CCL20 levels were higher in patients with hypercholesterolemia (18.5Ϯ3.2 versus 9.1Ϯ1.3 pg/mL; PϽ0.01). LDL induced the expression of CCL20 in VSMC in a dose-and time-dependent manner. Increased levels of CCL20 secreted by LDL-treated VSMC significantly induced human lymphocyte migration, an effect reduced by CCL20 silencing. The upregulation of CCL20 by LDL was dependent on the activation of kinase signaling pathways and NF-B. By site-directed mutagenesis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we identified a NF-B site (Ϫ80/Ϫ71) in CCL20 promoter critical for LDL responsiveness. Lysophosphatidic acid mimicked the upregulation of CCL20 induced by LDL, and minimal oxidation of LDL increased the ability of LDL to induce CCL20 through a mechanism that involves lysophosphatidic acid receptors. CCL20 was overexpressed in atherosclerotic lesions from coronary artery patients, colocalizing with VSMC. CCL20 was detected in conditioned media from healthy human aorta and its levels were significantly higher in secretomes from carotid endarterectomy specimens. A therosclerosis is essentially an inflammatory chronic disease. [1][2][3] Inflammation is a necessary response to injury and infection. Virtually all cardiovascular risk factors are capable of promoting an inflammatory response; among them, however, elevated levels of plasma cholesterol, in particular LDL, are recognized as one of the most important risk factors for atherosclerosis. 4,5 The inflammatory response involves the coordinated regulation of cell adhesion and migration and the establishment of a chemotactic gradient that guides inflammatory cells to damaged tissues. Key elements in this communication network are cytokines and chemokines, which orchestrate the recruitment, survival, expansion, and effector function of inflammatory cells. 6 -8 Chemokines are a superfamily of structurally related small chemotactic cytokines that control leukocyte function through interactions with their cognate 7-transmembranedomain G protein-coupled receptors. Monocytes/macrophages and T lymphocytes are the most abundant inflammatory cells found in atherosclerotic plaques, 9,10 but also B cells, dendritic cells, and neutrophils contribute to the pathogenesis of atherosclerosis. 9,11,12 Native and modified LDL modulate the expression of key genes involved in the recruitment and trafficking of inflammatory cells including cellular adhesion molecules and chemokines such as monocyte chemotactic protein 1. 4,5,[13][14][15] Recent studies have implicated other chemokines in atherosclerosis and have extended the knowledge about the regulation of chemokines/chemokine receptors on vascular cells, 6 -8 but the complete picture of these molecules involved in atherogenesis is not completely understood. Conclusion-ThisIncreasing data involving innate and adapti...

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In Vivo Low-Density Lipoprotein Exposure Induces Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Correlated With Activator Protein-1 Expression

Cited by 31 publications

References 36 publications

Vascular Adhesion Molecules in Atherosclerosis

Vascular Adhesion Molecules in Atherosclerosis

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

CCL20 Is Increased in Hypercholesterolemic Subjects and Is Upregulated By LDL in Vascular Smooth Muscle Cells

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