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ApoE Cx3cr1

Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
RATIONALE: Nonclassical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries. OBJECTIVE: This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions...
May 26, 2017: Circulation Research
Dhanya Ravindran, Anisyah Ridiandries, Laura Z Vanags, Rodney Henriquez, Siân Cartland, Joanne T M Tan, Christina A Bursill
Chemokines are important in macrophage recruitment and the progression of atherosclerosis. The 'M3' chemokine binding protein inactivates key chemokines involved in atherosclerosis (e.g. CCL2, CCL5 and CX3CL1). We aimed to determine the effect of M3 on plaque development and composition. In vitro chemotaxis studies confirmed that M3 protein inhibited the activity of chemokines CCL2, CCL5 and CX3CL1 as primary human monocyte migration as well as CCR2-, CCR5- and CX3CR1-directed migration was attenuated by M3...
2017: PloS One
Yao Wang, Yun-Shan Wang, Shu-Liang Song, Hao Liang, Ai-Guo Ji
Horny Goat Weed is a commonly used in Chinese herbal medicine. And it is used in multiple kinds of diseases including cardiovascular diseases. Icariin is the major component isolated from Horny Goat Weed. It is reported to have lipid-lowering effect. In atherosclerosis, icariin attenuate the enhanced prothrombotic state independently of its lipid-lowering effects. However, its detail mechanism is remaining unclear. This study aimed to investigate the effect and mechanism of icariin on atherosclerosis. We performed gene expression profiling on icariin treated LPS-stimulated RAW264...
February 19, 2016: Biochemical and Biophysical Research Communications
Ludovic Arnold, Hélène Perrin, Camille Baudesson de Chanville, Marielle Saclier, Patricia Hermand, Lucie Poupel, Elodie Guyon, Fabrice Licata, Wassila Carpentier, José Vilar, Rémi Mounier, Bénédicte Chazaud, Nora Benhabiles, Alexandre Boissonnas, Béhazine Combadiere, Christophe Combadiere
Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2(-/-) mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is upregulated in mice with efficient regeneration...
2015: Nature Communications
Lei Dong, Johannes Nordlohne, Shuwang Ge, Barbara Hertel, Anette Melk, Song Rong, Hermann Haller, Sibylle von Vietinghoff
Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe(-/-) (apolipoprotein E) CX3CR1(-/-) mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor-deficient (LDLr(-/-)) mice as well...
June 2016: Journal of the American Society of Nephrology: JASN
Olivier Levy, Sophie Lavalette, Shulong J Hu, Michael Housset, William Raoul, Chiara Eandi, José-Alain Sahel, Patrick M Sullivan, Xavier Guillonneau, Florian Sennlaub
UNLABELLED: Contrary to Alzheimer's disease (AD), the APOE2 allele increases and the APOE4 allele reduces the risk to develop age-related macular degeneration (AMD) compared with the most common APOE3 allele. The underlying mechanism for this association with AMD and the reason for the puzzling difference with AD are unknown. We previously demonstrated that pathogenic subretinal mononuclear phagocytes (MPs) accumulate in Cx3cr1-deficient mice due to the overexpression of APOE, interleukin-6, and CC chemokine ligand 2 (CCL2)...
October 7, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Alessandro Venosa, Rama Malaviya, Hyejeong Choi, Andrew J Gow, Jeffrey D Laskin, Debra L Laskin
Nitrogen mustard (NM) is an alkylating agent known to cause extensive pulmonary injury progressing to fibrosis. This is accompanied by a persistent macrophage inflammatory response. In these studies, we characterized the phenotype of macrophages accumulating in the lung over time following NM exposure. Treatment of rats with NM (0.125 mg/kg, intratracheally) resulted in an increase in CD11b(+) macrophages in histologic sections. These cells consisted of inducible nitric oxide synthase(+) (iNOS) proinflammatory M1 macrophages, and CD68(+), CD163(+), CD206(+), YM-1(+), and arginase-II(+)antiinflammatory M2 macrophages...
March 2016: American Journal of Respiratory Cell and Molecular Biology
Lin Gao, Zuojun Xu, Zhaofang Yin, Kan Chen, Changqian Wang, Huili Zhang
OBJECTIVES: Recent data in human and mice suggest that monocyte chemokine receptors CX3CR1 and CCR2 are involved in the pathogenesis of atherosclerosis. Our previous study showed that hydrogen sulfide, a novel gaseous mediator hampered the progression of atherosclerosis in fat-fed apoE(-/-) mice with downregulating CX3CR1 and CX3CL1 expressions. However, there is a paucity of information regarding the clinical association between endogenous H2S metabolism and alterations of monocyte chemokine receptors in patients with cardiovascular disease...
August 2015: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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
Wen-Hui Tsai, Chung-Hung Shih, Shan-Yu Feng, I-Ting Li, Shao-Chi Chang, Yu-Chieh Lin, Hui-Chi Hsu
BACKGROUND/AIMS: During the resolution phase of inflammation, release of "find-me" signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs) are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4) cells...
2014: Cellular Physiology and Biochemistry
Lucie Poupel, Alexandre Boissonnas, Patricia Hermand, Karim Dorgham, Elodie Guyon, Constance Auvynet, Flora Saint Charles, Philippe Lesnik, Philippe Deterre, Christophe Combadiere
OBJECTIVE: Alterations of the chemokine receptor CX3CR1 gene were associated with a reduced risk of myocardial infarction in human and limited atherosclerosis in mice. In this study, we addressed whether CX3CR1 antagonists are potential therapeutic tools to limit acute and chronic inflammatory processes in atherosclerosis. APPROACH AND RESULTS: Treatment with F1, an amino terminus-modified CX3CR1 ligand endowed with CX3CR1 antagonist activity, reduced the extent of atherosclerotic lesions in both Apoe(-/-) and Ldlr(-/-) proatherogenic mouse models...
October 2013: Arteriosclerosis, Thrombosis, and Vascular Biology
Emiel P C van der Vorst, Laura Z Vanags, Louise L Dunn, Hamish C Prosser, Kerry-Anne Rye, Christina A Bursill
The inflammatory chemokines CCL2, CCL5, and CX₃CL1 stimulate vascular smooth muscle cell (SMC) proliferation. High-density lipoproteins (HDLs) exhibit potent cardioprotective and anti-inflammatory properties. We therefore sought to determine the effect of reconstituted HDLs (rHDLs) on SMC chemokine expression and proliferation and elucidate the mechanisms. Preincubation of primary human SMCs with rHDLs containing apolipoprotein (apo)A-I and phosphatidylcholine (20 μM, final apoA-I concentration), before stimulation with TNF-α, inhibited CCL2 (54%), CCL5 (38%), and CX3CL1 (33%) protein levels...
April 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
Moritz Stolla, Jaroslav Pelisek, Marie-Luise von Brühl, Andreas Schäfer, Verena Barocke, Peter Heider, Michael Lorenz, Anca Tirniceriu, Alexander Steinhart, Johann Bauersachs, Paul F Bray, Steffen Massberg, Christian Schulz
Fractalkine (CX3CL1, FKN) is expressed in the inflamed vascular wall and absence of FKN reduces atherogenesis. Whether FKN is expressed throughout all stages of atherosclerotic disease and whether it directly contributes to monocyte recruitment to atherosclerotic lesions is not known. We collected human atherosclerotic plaque material and blood samples from patients with carotid artery disease undergoing endarterectomy. Plaques were analyzed by immunohistochemistry and qPCR. We found that FKN is expressed at all stages of atherosclerotic lesion formation, and that the number of FKN-expressing cells positively correlates with the number of CX3CR1-positive cells in human carotid artery plaques...
2012: PloS One
Stephen A Spector, Kumud K Singh, Saurabh Gupta, Lucette A Cystique, Hua Jin, Scott Letendre, Rachel Schrier, Zunyou Wu, Kun X Hong, Xin Yu, Chuan Shi, Robert K Heaton
BACKGROUND: Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese individuals infected through contaminated blood products. METHODS: Two hundred and one HIV-infected patients from Anhui, China, had neuropsychological tests at baseline and 12 months. DNA was genotyped for APOE epsilon2, epsilon3 and epsilon4 alleles; MBL2-A/O; CCR5-wt/Delta32; CCR5-59029-G/A; CCR2-180-G/A; SDF-1-G/A; IL4-589-C/T; MCP-1-2518-A/G; CX3CR1-745-G/A; -849-C/T polymorphisms and CCL3L1 copy number variants using real-time PCR...
June 19, 2010: AIDS
Katarzyna Janik-Papis, Małgorzata Zaraś, Anna Skłodowska, Magdalena Ulińska, Anna I Borucka, Janusz Błasiak
Age-related macular degeneration (AMD) is a progressive disease characterized in macula photoreceptors degeneration that leads to loss of central vision in elderly people, especially in developed countries. Many environmental and genetic factors have influence on the occurrence and progression of AMD as well as its form: either dry or exudative. Despite of the extensive research, etiology and molecular background of AMD are poorly understood. Due to advanced biochemical and biophysical techniques some clinical aspects of AMD have been described in details, however, the genetic basis of AMD is still under investigation...
2009: Klinika Oczna
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