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apoe knockout cx3cr1

Talin Ebrahimian, David Simon, Catherine A Lemarié, Stefania Simeone, Maryam Heidari, Koren K Mann, Sven Wassmann, Stephanie Lehoux
OBJECTIVE: Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates cell survival, migration, and inflammatory response, but its role in atherogenesis is unknown. APPROACH AND RESULTS: To investigate the role of FHL2 in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to generate ApoE/FHL2-/- mice. After high-fat diet, ApoE/FHL2-/- mice had significantly smaller atherosclerotic plaques than ApoE-/- mice in the aortic sinus, the brachiocephalic artery, and the aorta...
May 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Olivier Levy, Bertrand Calippe, Sophie Lavalette, Shulong J Hu, William Raoul, Elisa Dominguez, Michael Housset, Michel Paques, José-Alain Sahel, Alexis-Pierre Bemelmans, Christophe Combadiere, Xavier Guillonneau, Florian Sennlaub
Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1(-/-) mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE...
February 2015: EMBO Molecular Medicine
Peter J Psaltis, Amrutesh S Puranik, Daniel B Spoon, Colin D Chue, Scott J Hoffman, Tyra A Witt, Sinny Delacroix, Laurel S Kleppe, Cheryl S Mueske, Shuchong Pan, Rajiv Gulati, Robert D Simari
RATIONALE: Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. OBJECTIVE: We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. METHODS AND RESULTS: Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units...
July 18, 2014: Circulation Research
Peng Nie, Dandan Li, Liuhua Hu, Shuxuan Jin, Ying Yu, Zhaohua Cai, Qin Shao, Jieyan Shen, Jing Yi, Hua Xiao, Linghong Shen, Ben He
It is well documented that statins protect atherosclerotic patients from inflammatory changes and plaque instability in coronary arteries. However, the underlying mechanisms are not fully understood. Using a previously established mouse model for vulnerable atherosclerotic plaque, we investigated the effect of atorvastatin (10 mg/kg/day) on plaque morphology. Atorvastatin did not lower plasma total cholesterol levels or affect plaque progression at this dosage; however, vulnerable plaque numbers were significantly reduced in the atorvastatin-treated group compared to control...
2014: PloS One
Sergio Martínez-Hervás, Angela Vinué, Laura Núñez, Irene Andrés-Blasco, Laura Piqueras, José Tomás Real, Juan Francisco Ascaso, Deborah Jane Burks, María Jesús Sanz, Herminia González-Navarro
AIMS: Insulin resistance (IR) is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events are mainly due to rupture of unstable plaques, and the role of vascular smooth muscle cells (VSMCs) in this process in IR, Type 2 diabetes mellitus, and metabolic syndrome (T2DM/MetS) has not been fully addressed. Therefore, the role of VSMC survival in the generation of unstable plaques in T2DM/MetS and the involvement of inflammatory mediators was investigated...
July 15, 2014: Cardiovascular Research
Huili Zhang, Changfa Guo, Alian Zhang, Yuqi Fan, Ting Gu, Duojiao Wu, Anna Sparatore, Changqian Wang
Hydrogen sulfide (H(2)S) is a novel gaseous mediator that plays important roles in atherosclerosis. The present study investigated the effect of a novel H(2)S-releasing aspirin, ACS14 (2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester), on atherosclerotic plaques in fat-fed apoE(-/-) mice and the underlying mechanism with respect to CX3C chemokine receptor 1 (CX3CR1) in macrophages. Mouse macrophage cell line RAW264.7 or mouse peritoneal macrophages were preincubated with aspirin (50, 100 or 200μM), ACS14 (50, 100 or 200μM) or vehicle for 6h, and then stimulated with interferon (IFN)-γ (500U/ml) or lipopolysaccharide (LPS; 10μg/ml) for 12h...
December 15, 2012: European Journal of Pharmacology
Noah Saederup, Liana Chan, Sergio A Lira, Israel F Charo
BACKGROUND: Monocyte-derived foam cells are the hallmark of early atherosclerosis, and recent evidence indicates that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Genetic deletions of monocyte chemoattractant protein-1 (MCP-1, CCL2), fractalkine (CX3CL1), or their cognate receptors, CCR2 and CX3CR1, markedly reduce atherosclerotic lesion size in murine models of atherosclerosis. The aim of this study was to determine whether these 2 chemokines act independently or redundantly in promoting atherogenesis...
April 1, 2008: Circulation
Peng Liu, Yen-Rei A Yu, Jessica A Spencer, Ashley E Johnson, Christopher T Vallanat, Alan M Fong, Cam Patterson, Dhavalkumar D Patel
OBJECTIVE: Dendritic cells (DCs) have recently been found in atherosclerosis-predisposed regions of arteries and have been proposed to be causal in atherosclerosis. The chemokine receptor CX3CR1 is associated with arterial injury and atherosclerosis. We sought to determine whether a link exists between arterial DC accumulation, CX3CR1, and atherosclerosis. METHODS AND RESULTS: Mouse aortas were isolated and subjected to en face immunofluorescence analysis. We found that DCs were located predominantly in the intimal regions of arterial branch points and curvatures...
February 2008: Arteriosclerosis, Thrombosis, and Vascular Biology
Miha Cercek, Michiaki Matsumoto, Hongyan Li, Kuang-Yuh Chyu, Ashok Peter, Prediman K Shah, Paul C Dimayuga
Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression...
January 13, 2006: Biochemical and Biophysical Research Communications
Daniel Teupser, Stephanos Pavlides, Marietta Tan, Jose-Carlos Gutierrez-Ramos, Roland Kolbeck, Jan L Breslow
Fractalkine (CX3CL1) is of particular interest in atherogenesis because it can serve as an adhesion molecule and a chemokine. Fractalkine and its receptor CX3CR1 are expressed in atherosclerotic lesions of humans and mice. However, the effect of fractalkine deficiency on atherosclerosis susceptibility is unknown. Fractalkine-deficient mice on the C57BL/6 (B6) background were bred to the atherosclerosis-sensitizing B6.ApoE(-/-) and B6.LDLR(-/-) backgrounds. Compared with controls, aortic-root lesion area was unchanged in fractalkine-deficient male and female B6...
December 21, 2004: Proceedings of the National Academy of Sciences of the United States of America
Christophe Combadière, Stéphane Potteaux, Ji-Liang Gao, Bruno Esposito, Saveria Casanova, Eric J Lee, Patrice Debré, Alain Tedgui, Philip M Murphy, Ziad Mallat
BACKGROUND: Fractalkine (CX3CL1), a CX3C chemokine, is expressed in the vessel wall and mediates the firm adhesion and chemotaxis of leukocytes expressing its receptor, CX3CR1. A polymorphism in the CX3CR1 gene is associated with low CX3CR1 expression and reduced risk of acute coronary disease in humans. METHODS AND RESULTS: We generated CX3CR1-deficient mice (CX3CR1(-/-)) by targeted gene disruption and crossed them with the proatherogenic apolipoprotein E-deficient mice (apoE(-/-))...
February 25, 2003: Circulation
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