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macrophage and atherogenesis

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https://www.readbyqxmd.com/read/28209797/roles-of-vascular-oxidative-stress-and-nitric-oxide-in-the-pathogenesis-of-atherosclerosis
#1
REVIEW
Ulrich Förstermann, Ning Xia, Huige Li
Major reactive oxygen species (ROS)-producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis...
February 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28209562/vinexin-%C3%AE-ablation-inhibits-atherosclerosis-in-apolipoprotein-e-deficient-mice-by-inactivating-the-akt-nuclear-factor-%C3%AE%C2%BAb-inflammatory-axis
#2
Hongjing Guan, Wen-Lin Cheng, Junhong Guo, Meng-Lin Chao, Yan Zhang, Jun Gong, Xue-Yong Zhu, Zhi-Gang She, Zan Huang, Hongliang Li
BACKGROUND: Vinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown. METHODS AND RESULTS: Immunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining...
February 16, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28173800/oxidized-ldl-induced-jab1-influences-nf-%C3%AE%C2%BAb-independent-inflammatory-signaling-in-human-macrophages-during-foam-cell-formation
#3
Anja Schwarz, Gabriel A Bonaterra, Hans Schwarzbach, Ralf Kinscherf
BACKGROUND: Oxidized low-density lipoprotein (oxLDL) mediates the transformation of macrophages (MΦ) to cholesterol-rich foam cells and the release of pro-inflammatory cytokines during atherogenesis. JAB1 (Jun activation domain binding protein-1) is present in all stages of human plaques, involved in the Toll-like receptor-mediated activation of p38 mitogen-activated protein kinase (MAPK) and controls nuclear factor-kappa B (NF-κB) activation. Thus, we were interested in the role of JAB1 during foam cell formation of MΦ after oxLDL exposition...
February 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28137963/the-role-of-efferocytosis-in-atherosclerosis
#4
Yoko Kojima, Irving L Weissman, Nicholas J Leeper
The necrotic core has long been a hallmark of the vulnerable atherosclerotic plaque. Although apoptotic cells are cleared quickly in almost all other tissue beds, their removal appears to be significantly impaired in the diseased blood vessel. Emerging evidence indicates that this phenomenon is caused by a defect in efferocytosis, the process by which apoptotic tissue is recognized for engulfment by phagocytic cells such as macrophages. Genetic and experimental data suggest that efferocytosis is impaired during atherogenesis caused by dysregulation of so-called eat me ligands, which govern the edibility of cells undergoing programmed cell death...
January 31, 2017: Circulation
https://www.readbyqxmd.com/read/28124601/use-of-primary-macrophages-for-searching-novel-immunocorrectors
#5
N G Nikiforov, N V Elizova, M Bukrinsky, L Dubrovsky, V J Makeev, Y Wakabayashi, P Liu, K K Foxx, H S Kruth, X Jin, E R Zakiev, A N Orekhov
In this mini-review, the role of macrophage phenotypes in atherogenesis is considered. Recent studies on distribution of M1 and M2 macrophages in different types of atherosclerotic lesions indicate that macrophages exhibit a high degree of plasticity of phenotype in response to various conditions in microenvironment. The effect of the accumulation of cholesterol, a key event in atherogenesis, on the macrophage phenotype is also discussed. The article presents the results of transcriptome analysis of cholesterol-loaded macrophages revealing genes involved in immune response whose expression rate has changed the most...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28122883/retinol-binding-protein-dependent-cholesterol-uptake-regulates-macrophage-foam-cell-formation-and-promotes-atherosclerosis
#6
Yan Liu, Yuan Zhong, Hongen Chen, Duan Wang, Min Wang, Jing-Song Ou, Min Xia
BACKGROUND: -Retinol binding protein 4 (RBP4) is an adipokine that plays decisive roles in glucose metabolism and insulin sensitivity. Elevated circulating RBP4 levels were reported to be associated with increased risk for cardiovascular disease, but the precise role of RBP4 in atherosclerotic diseases and its mechanisms of action remain elusive. METHODS: -Serum RBP4 levels of 1683 participants from South China were evaluated and the occurrence of major adverse cardiovascular events was followed up for 5 years...
January 25, 2017: Circulation
https://www.readbyqxmd.com/read/28115514/ablation-of-interferon-regulatory-factor-3-protects-against-atherosclerosis-in-apolipoprotein-e-deficient-mice
#7
Hui Liu, Wen-Lin Cheng, Xi Jiang, Pi-Xiao Wang, Chun Fang, Xue-Yong Zhu, Zan Huang, Zhi-Gang She, Hongliang Li
The secretion of adhesion molecules by endothelial cells, as well as the subsequent infiltration of macrophages, determines the initiation and progression of atherosclerosis. Accumulating evidence suggests that IRF3 (interferon regulatory factor 3) is required for the induction of proinflammatory cytokines and for endothelial cell proliferation. However, the effect and underlying mechanism of IRF3 on atherogenesis remain unknown. Our results demonstrated a moderate-to-strong immunoreactivity effect associated with IRF3 in the endothelium and macrophages of the atherosclerotic plaques in patients with coronary heart disease and in hyperlipidemic mice...
March 2017: Hypertension
https://www.readbyqxmd.com/read/28069704/angiopoietin-1-promotes-atherosclerosis-by-increasing-the-proportion-of-circulating-gr1-monocytes
#8
Takeshi Fujisawa, Keqing Wang, Xi-Lin Niu, Stuart Egginton, Shakil Ahmad, Peter Hewett, Christopher D Kontos, Asif Ahmed
AIMS: Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse...
January 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28063350/deficiency-of-scavenger-receptor-class-b-type-1-leads-to-increased-atherogenesis-with-features-of-advanced-fibroatheroma-and-expansive-arterial-remodeling
#9
Jiawei Liao, Xin Guo, Mengyu Wang, Mingming Gao, Qiang Shen, Yuhui Wang, Wei Huang, George Liu
BACKGROUND: Scavenger receptor class B type 1 (SR-BI) is the main high-density lipoprotein (HDL) receptor in mammalians. Loss of SR-BI has been proven to disturb HDL metabolism and accelerate atherosclerosis. However, little is known about the plaque features and arterial remodeling in the increased atherogenesis caused by SR-BI deficiency. Here, we explored this issue in atherosclerosis-prone low-density lipoprotein receptor (LDL-R) knockout (KO) mice deficient of SR-BI. METHODS AND RESULTS: SR-BI/LDL-R double KO (dKO) and control LDL-R KO mice were fed an atherogenic diet for 12 weeks...
December 22, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28039493/new-markers-in-atherosclerosis-thrombospondin-2-thbs-2-and-leukocyte-cell-derived-chemotaxin-2-lect-2-an-immunohistochemical-study
#10
Fatma Cavide Sonmez, Pelin Yildiz, Muhammad Salman Akhtar, Cemalettin Aydin, Osman Sonmez, Nuray Ay, Mehmet Akif Vatankulu
BACKGROUND Current research investigating the role of THBS2 and LECT-2 in atherogenesis is very limited. Therefore, we designed this study to demonstrate the role of THBS-2 and LECT-2 in atherosclerosis at the tissue level in fresh specimens. MATERIAL AND METHODS A total of 32 patients who underwent coronary bypass surgery were enrolled. Aortic wall punch biopsies were obtained at the site of proximal aortosaphenous bypass graft anastomosis. A specimen of left internal mammarian artery (LiMA) was taken from the segment just proximal to its anastomosis...
December 31, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28034277/the-two-faces-of-interleukin-17a-in-atherosclerosis-interleukin-17a-and-atherosclerosis
#11
Mohammadreza Akhavanpoor, Hamidreza Akhavanpoor, Christian A Gleissner, Susanne Wangler, Andreas O Doesch, Hugo A Katus, Christian Erbel
A complex network of different cytokines and chemokines modulate atherosclerosis, a chronic inflammatory disease. Interleukin-17A (IL-17A) is expressed by different leukocyte subsets such as CD4+IL-17+ T cells (Th17), γδ T cells, natural killer cells, natural killer T cells, and neutrophils. IL-17A plays an important role in host defense and is involved in the pathology of different autoimmune and inflammatory diseases. Recent studies demonstrate an association of IL-17A with atherosclerosis. IL-17A seems to have primarily pro-inflammatory effects in atherogenesis, although there are partially controversial results in the literature...
December 29, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28009484/hsp90-inhibition-suppresses-inflammatory-response-and-reduces-carotid-atherosclerotic-plaque-formation-in-apoe-mice
#12
Hongmei Mu, Liyong Wang, Lei Zhao
AIM: Emerging evidences indicate that heat shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In the present study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature. METHODS: HSP90-overexpression lentivirus (Lenti-HSP90) was used to transfect apoE(-/-) mice after constrictive collars were planted at the right common carotid arteries. RESULTS: As a result, HSP90 gene overexpression led to reduction in en face plaque area, and increase in unstable plaque with heavier accumulation of lipids...
December 23, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27995417/high-density-lipoprotein-from-subjects-with-coronary-artery-disease-promotes-macrophage-foam-cell-formation-role-of-scavenger-receptor-cd36-and-erk-mapk-signaling
#13
S Sini, D Deepa, S Harikrishnan, N Jayakumari
Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content...
March 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27993833/nkx2-5-is-expressed-in-atherosclerotic-plaques-and-attenuates-development-of-atherosclerosis-in-apolipoprotein-e-deficient-mice
#14
Meng Du, Xiaojing Wang, Xin Tan, Xiangrao Li, Dandan Huang, Kun Huang, Liu Yang, Fengxiao Zhang, Yan Wang, Dan Huang, Kai Huang
BACKGROUND: NK2 homeobox 5 (Nkx2-5) is a cardiac homeobox transcription factor that is expressed in a broad range of cardiac sublineages. Embryos lacking Nkx2-5 are nonviable attributed to growth retardation and gross abnormalities of the heart. However, the role of Nkx2-5 in atherosclerosis remains elusive. This study aims to elucidate the specific functions of Nkx2-5 during atherogenesis and in established atherosclerotic plaques. METHODS AND RESULTS: Two types of atherosclerotic lesions were created in ApoE(-/-) mice through 2 different dietary manipulations...
December 19, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27924297/datasets-for-the-validation-of-the-in-vivo-sirna-silencing-of-cd40-and-for-the-detection-of-new-markers-of-atherosclerosis-progression-in-apoe-deficient-mice
#15
Miguel Hueso, Laura De Ramon, Estanislao Navarro, Elia Ripoll, Josep M Cruzado, Josep M Grinyo, Joan Torras
Data presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016) [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE(-/-) mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80(+), galectin-3(+) macrophages or by NF-κB(+) cells...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27910925/thrombomodulin-regulates-monocye-differentiation-via-pkc%C3%AE-and-erk1-2-pathway-in-vitro-and-in-atherosclerotic-artery
#16
Chien-Sung Tsai, Yi-Wen Lin, Chun-Yao Huang, Chun-Min Shih, Yi-Ting Tsai, Nai-Wen Tsao, Chin-Sheng Lin, Chun-Che Shih, Hellen Jeng, Feng-Yen Lin
Thrombomodulin (TM) modulates the activation of protein C and coagulation. Additionally, TM regulates monocyte migration and inflammation. However, its role on monocyte differentiation is still unknown. We investigated the effects of TM on monocyte differentiation. First, we found that TM was increased when THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA). Overexpression of TM enhanced the macrophage markers, CD14 and CD68 expression in PMA-induced THP-1. TM siRNA depressed the PMA-induced increase of p21(Cip1/WAF1) via ERK1/2-NF-kB p65 signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871915/inhibition-of-siglec-1-by-lentivirus-mediated-small-interfering-rna-attenuates-atherogenesis-in-apoe-deficient-mice
#17
Yi-Song Xiong, Ai-Lin Wu, Dong Mu, Juan Yu, Ping Zeng, Yi Sun, Jie Xiong
BACKGROUND: Siglec-1 is highly expressed on circulating monocytes and plaque macrophages in atherosclerotic patients, but the exact role of Siglec-1 in atherosclerosis has not been elucidated. METHODS: Lentiviral vector containing small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv-shNC) were injected intravenously into 6-week old Apoe(-/-) mice. Then onset of atherosclerosis was observed. RESULTS: Siglec-1 was highly expressed in aortic plaques and it can be down-regulated by Lv-shSiglec-1 injection...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27871059/selective-p38%C3%AE-map-kinase-mapk14-inhibition-in-enzymatically-modified-ldl-stimulated-human-monocytes-implications-for-atherosclerosis
#18
Fei Cheng, Laura Twardowski, Sarah Fehr, Christoph Aner, Elke Schaeffeler, Thomas Joos, Thomas Knorpp, Bernhard Dorweiler, Stefan Laufer, Matthias Schwab, Michael Torzewski
The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27869741/isoliquiritigenin-attenuates-atherogenesis-in-apolipoprotein-e-deficient-mice
#19
Fen Du, Quzhen Gesang, Jia Cao, Mei Qian, Li Ma, Dongfang Wu, Hong Yu
Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS)...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27856455/map3k8-modulates-monocyte-state-and-atherogenesis-in-apoe-mice
#20
Carlos Sanz-Garcia, Ángela Sánchez, Constanza Contreras-Jurado, Carmela Cales, Cristina Barranquero, Marta Muñóz, Ramón Merino, Paula Escudero, Maria-Jesús Sanz, Jesús Osada, Ana Aranda, Susana Alemany
OBJECTIVE: Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS: We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD)...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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