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macrophage and atherogenesis

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https://www.readbyqxmd.com/read/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#1
Somasundaram Raghavan, Nikhlesh K Singh, Arul M Mani, Gadiparthi N Rao
Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin-Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3-mediated ubiquitination and degradation of ATP-binding cassette subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29772480/proteoglycan-4-regulates-macrophage-function-without-altering-atherosclerotic-lesion-formation-in-a-murine-bone-marrow-specific-deletion-model
#2
Joya E Nahon, Menno Hoekstra, Stefan R Havik, Peter J Van Santbrink, Geesje M Dallinga-Thie, Jan-Albert Kuivenhoven, Janine J Geerling, Miranda Van Eck
BACKGROUND AND AIMS: Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. METHODS: The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined...
May 5, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29750307/exosomal-malat1-derived-from-oxidized-low-density-lipoprotein-treated-endothelial-cells-promotes-m2-macrophage-polarization
#3
Chaoyang Huang, Jie Han, Yutao Wu, Shan Li, Qiwen Wang, Wenjuan Lin, Jianhua Zhu
Oxidized low-density lipoprotein (oxLDL)-induced injury and apoptosis of endothelial cells are important initial events in numerous cardiovascular diseases. Following activation by oxLDL, monocytes adhere to endothelial cells, migrate into the subendothelial spaces and then undergo differentiation into macrophages, which subsequently induces the formation of atherosclerotic lesions. However, the mechanisms underlying the activation of macrophage differentiation by oxLDL-treated endothelial cells remain unclear...
May 7, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29737246/role-of-ox-ldl-and-lox-1-in-atherogenesis
#4
Ajoe John Kattoor, Sri Harsha Kanuri, Jawahar L Mehta
Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox-LDL through LOX-1, in endothelial cells, cause increase in leukocyte adhesion molecules, activates pathways of apoptosis, increase reactive oxygen species and cause endothelial dysfunction...
May 7, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29726984/immune-cell-census-in-murine-atherosclerosis-cytometry-by-time-of-flight-illuminates-vascular-myeloid-cell-diversity
#5
Jennifer E Cole, Inhye Park, David Ahern, Christina Kassiteridi, Dina Danso Abeam, Michael Goddard, Patricia Green, Pasquale Maffia, Claudia Monaco
Aims: Atherosclerosis is characterised by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks...
May 2, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29724817/myeloid-%C3%AE-catenin-deficiency-exacerbates-atherosclerosis-in-low-density-lipoprotein-receptor-deficient-mice
#6
Fang Wang, Zun Liu, Se-Hyung Park, Taesik Gwag, Weiwei Lu, Murong Ma, Yipeng Sui, Changcheng Zhou
OBJECTIVE: The Wnt/β-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/β-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage β-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of β-catenin expression on macrophage functions and atherosclerosis development...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29701665/adropin-contributes-to-anti-atherosclerosis-by-suppressing-monocyte-endothelial-cell-adhesion-and-smooth-muscle-cell-proliferation
#7
Kengo Sato, Tomoyuki Yamashita, Remina Shirai, Koichiro Shibata, Taisuke Okano, Maho Yamaguchi, Yusaku Mori, Tsutomu Hirano, Takuya Watanabe
Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro and atherogenesis in Apoe -/- mice in vivo...
April 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29700120/protease-activated-receptor-2-plays-a-critical-role-in-vascular-inflammation-and-atherosclerosis-in-apolipoprotein-e-deficient-mice
#8
Tomoya Hara, Pham Tran Phuong, Daiju Fukuda, Koji Yamaguchi, Chie Murata, Sachiko Nishimoto, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Issei Imoto, Michio Shimabukuro, Masataka Sata
Background -The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X (FXa), are expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. Methods -We generated apolipoprotein E-deficient ( ApoE-/- ) mice lacking systemic PAR-2 expression ( ApoE-/- PAR-2-/- )...
April 26, 2018: Circulation
https://www.readbyqxmd.com/read/29695588/mindin-deficiency-in-macrophages-protects-against-foam-cell-formation-and-atherosclerosis-by-targeting-lxr-%C3%AE
#9
Cheng Zhang, Juan-Juan Qin, Fu-Han Gong, Jing-Jing Tong, Wen-Lin Cheng, Haiping Wang, Yan Zhang, Xueyong Zhu, Zhi-Gang She, Hao Xia, Li-Hua Zhu
Abstract Background - Mindin, which is a highly conserved ECM protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes and immune responses. The aim of this study was to assess whether mindin contributes to the development of atherosclerosis. Methods and Results - A significant upregulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/-  mice after HFD treatment. Mindin-/- ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis...
April 25, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29687414/m1-macrophages-but-not-m2-macrophages-are-characterized-by-upregulation-of-crp-expression-via-activation-of-nf%C3%AE%C2%BAb-a-possible-role-for-ox-ldl-in-macrophage-polarization
#10
Marielle Kaplan, Anna Shur, Yvgeny Tendler
Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression...
April 23, 2018: Inflammation
https://www.readbyqxmd.com/read/29684642/innate-and-adaptive-immunity-in-atherosclerosis
#11
REVIEW
Kapka Miteva, Rosalinda Madonna, Raffaele De Caterina, Sophie Van Linthout
Atherosclerosis is a chronic inflammatory disorder of the large and medium-size arteries characterized by the subendothelial accumulation of cholesterol, immune cells, and extracellular matrix. At the early onset of atherogenesis, endothelial dysfunction takes place. Atherogenesis is further triggered by the accumulation of cholesterol-carrying low-density lipoproteins, which acquire properties of damage-associated molecular patterns and thereby trigger an inflammatory response. Following activation of the innate immune response, mainly governed by monocytes and macrophages, the adaptive immune response is started which further promotes atherosclerotic plaque formation...
April 20, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29674474/genetic-deletion-of-il-interleukin-19-exacerbates-atherogenesis-in-il19-%C3%A3-ldlr-double-knockout-mice-by-dysregulation-of-mrna-stability-protein-hur-human-antigen-r
#12
Mitali Ray, Khatuna Gabunia, Christine N Vrakas, Allison B Herman, Farah Kako, Sheri E Kelemen, Laurel A Grisanti, Michael V Autieri
OBJECTIVE: To test the hypothesis that loss of IL (interleukin)-19 exacerbates atherosclerosis. APPROACH AND RESULTS: Il19 -/- mice were crossed into Ldlr -/- (low-density lipoprotein receptor knock out) mice. Double knockout (dKO) mice had increased plaque burden in aortic arch and root compared with Ldlr -/- controls after 14 weeks of high-fat diet (HFD). dKO mice injected with 10 ng/g per day rmIL-19 had significantly less plaque compared with controls. qRT-PCR and Western blot analysis revealed dKO mice had increased systemic and intraplaque polarization of T cells and macrophages to proinflammatory Th 1 and M1 phenotypes, and also significantly increased TNF (tumor necrosis factor)-α expression in spleen and aortic arch compared with Ldlr -/- controls...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29656494/oxidized-ldl-phagocytosis-during-foam-cell-formation-in-atherosclerotic-plaques-relies-on-a-pld2-cd36-functional-interdependence
#13
Ramya Ganesan, Karen M Henkels, Lucile E Wrenshall, Yasunori Kanaho, Gilbert Di Paolo, Michael A Frohman, Julian Gomez-Cambronero
The uptake of cholesterol carried by low-density lipoprotein (LDL) is tightly controlled in the body. Macrophages are not well suited to counteract the cellular consequences of excess cholesterol leading to their transformation into "foam cells," an early step in vascular plaque formation. We have uncovered and characterized a novel mechanism involving phospholipase D (PLD) in foam cell formation. Utilizing bone marrow-derived macrophages from genetically PLD deficient mice, we demonstrate that PLD2 (but not PLD1)-null macrophages cannot fully phagocytose aggregated oxidized LDL (Agg-Ox-LDL), which was phenocopied with a PLD2-selective inhibitor...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29617722/pcsk9-regulates-expression-of-scavenger-receptors-and-ox-ldl-uptake-in-macrophages
#14
Zufeng Ding, Shijie Liu, Xianwei Wang, Sue Theus, Xiaoyan Deng, Yubo Fan, Sichang Zhou, Jawahar L Mehta
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to influence macrophage biology and modulate atherogenesis. We conducted this study to examine the regulation of scavenger receptors (SRs) (LOX-1, SRA, and CD36) and oxidized liporoptein cholesterol (ox-LDL) uptake in macrophages by PCSK9. Methods and results: Treatment of mouse peritoneal macrophages with tumour necrosis factor alpha (TNF-α) resulted in concentration-dependent modest, but significant, increase in PCSK9 expression...
March 29, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29601312/myeloid-cells-regulate-plasma-ldl-cholesterol-levels
#15
Venetia Bazioti, Anouk M La Rose, Marit Westerterp
PURPOSE OF REVIEW: Leukocytosis, elevated blood leukocyte levels, is associated with enhanced cardiovascular risk in humans. Hematopoietic stem and progenitor cells (HSPCs) drive leukocyte production in a process called hematopoiesis, which mainly occurs in the bone marrow, and under certain conditions also in other organs such as the spleen. Cholesterol accumulation in HSPCs enhances hematopoiesis, increasing levels of blood monocytes that infiltrate into atherosclerotic plaques. Although HSPC proliferation and monocytosis enhance atherogenesis in several studies, concomitant decreases in LDL-cholesterol levels have also been reported, associated with anti-atherogenic effects...
March 29, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29589525/impact-of-dysfunctional-protein-catabolism-on-macrophage-cholesterol-handling
#16
Takuro Miyazaki, Akira Miyazaki
Protein catabolism in macrophages, which is accomplished mainly through autophagy-lysosomal degradation, ubiquitin-proteasome system, and calpains, is disturbed in atheroprone vessels. Moreover, growing evidence suggests that defects in protein catabolism interfere with cholesterol handling in macrophages. Indeed, decreases in autophagy facilitate the deposition of cholesterol in atheroprone macrophages and the subsequent development of vulnerable atherosclerotic plaques due to impaired catabolism of lipid droplets and limited efferocytic clearance of deadly cells...
March 26, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29588315/cholesterol-efflux-pathways-suppress-inflammasome-activation-netosis-and-atherogenesis
#17
Marit Westerterp, Panagiotis Fotakis, Mireille Ouimet, Andrea E Bochem, Hanrui Zhang, Matthew M Molusky, Wei Wang, Sandra Abramowicz, Sacha la Bastide-van Gemert, Nan Wang, Carrie L Welch, Muredach P Reilly, Erik S Stroes, Kathryn J Moore, Alan R Tall
Background -The CANTOS trial showed that antagonism of interleukin-1β (IL-1β) reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk. IL-1β and IL-18 secretion are produced via the NLRP3 inflammasome in myeloid cells in response to cholesterol accumulation, but mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear. The cholesterol transporters ATP Binding Cassette A1 and G1 (ABCA1/G1) mediate cholesterol efflux to high-density-lipoprotein (HDL) and Abca1/g1 deficiency in myeloid cells leads to cholesterol accumulation...
March 27, 2018: Circulation
https://www.readbyqxmd.com/read/29560080/hydrogen-sulfide-abrogates-hemoglobin-lipid-interaction-in-atherosclerotic-lesion
#18
László Potor, Péter Nagy, Gábor Méhes, Zoltán Hendrik, Viktória Jeney, Dávid Pethő, Anita Vasas, Zoltán Pálinkás, Enikő Balogh, Ágnes Gyetvai, Matthew Whiteman, Roberta Torregrossa, Mark E Wood, Sándor Olvasztó, Péter Nagy, György Balla, József Balla
The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase- (CSE-) derived H2 S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29551552/non-coding-rna-regulation-of-endothelial-and-macrophage-functions-during-atherosclerosis
#19
REVIEW
Binod Aryal, Yajaira Suárez
The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis...
March 15, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29549823/microrna-98-regulates-foam-cell-formation-and-lipid-accumulation-through-repression-of-lox-1
#20
Yao Dai, Xiaoqin Wu, Dongsheng Dai, Jun Li, Jawahar L Mehta
OBJECTIVE: Several miR/s that regulate gene/s relevant in atherogenesis are being described. We identified a miR (miR-98) that targets LOX-1, a receptor for ox-LDL, and speculated that it might be relevant in atherogenesis. APPROACH AND RESULTS: MicroRNA-98 was predicted by bioinformatics tools. The effects of miR-98 (by use of mimics and inhibitors) on LOX-1 expression and foam cell formation in mouse peritoneal macrophages were assessed. ApoE-/- mice fed by high fat diet were administered with mmu-agomiR-98 and mmu-antagomiR-98, and expression of LOX-1 and foam cell formation in aorta were quantified...
March 8, 2018: Redox Biology
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