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https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#1
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202387/varenicline-enhances-oxidized-ldl-uptake-by-increasing-expression-of-lox-1-and-cd36-scavenger-receptors-through-%C3%AE-7-nachr-in-macrophages
#2
Yuki Kanaoka, Mitsuhisa Koga, Keita Sugiyama, Kaoru Ohishi, Yasufumi Kataoka, Atsushi Yamauchi
Varenicline is a widely used and effective drug for smoking cessation. It is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and full agonist of α7 nAChR. We have reported that varenicline aggravates formation of atherosclerotic plaques through α7 nAChR in apolipoprotein E knockout mice. However, little is known about its effects on macrophages in atherosclerotic plaques. Here, we ascertained whether varenicline promotes oxidized low-density lipoprotein (oxLDL) uptake in mouse peritoneal macrophages in vitro and clarified its mechanism...
February 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28199510/endothelial-lox-1-activation-differentially-regulates-arterial-thrombus-formation-depending-on-oxldl-levels-role-of-the-oct-1-sirt1-and-erk1-2-pathways
#3
Alexander Akhmedov, Giovanni G Camici, Martin F Reiner, Nicole Bonetti, Sarah Costantino, Erik W Holy, Remo D Spescha, Simona Stivala, Ariane Schaub Clerigué, Thimoteus Speer, Alexander Breitenstein, Jasmin Manz, Christine Lohmann, Francesco Paneni, Juerg-Hans Beer, Thomas F Lüscher
No abstract text is available yet for this article.
February 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28182779/o-prenylated-3-carboxycoumarins-as-a-novel-class-of-15-lox-1-inhibitors
#4
Atena Jabbari, Mina Mousavian, Seyed Mohamad Seyedi, Mehdi Bakavoli, Hamid Sadeghian
Allyloxy, Isopentenyloxy, geranyloxy and farnesyloxy derivatives of 3-carboxycoumarin, at position 5, 6, 7, and 8, were synthesized and their inhibitory potency against human 15-lipoxygenase-1 (human 15-LOX-1) were determined. Among the synthetic coumarins, O-allyl and O-isopentenyl derivatives demonstrated no considerable lipoxygenase inhibition while O-geranyl and O-farnesyl derivatives demonstrated potent inhibitory activity. 5-farnesyloxy-3-carboxycoumarin demonstrated the most potent inhibitory activity by IC50 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28146073/lox-1-and-its-splice-variants-a-new-challenge-for-atherosclerosis-and-cancer-targeted-therapies
#5
REVIEW
Barbara Rizzacasa, Elena Morini, Sabina Pucci, Michela Murdocca, Giuseppe Novelli, Francesca Amati
Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both "risk" and "protective" splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28108289/negative-feedback-regulation-between-microrna-let-7g-and-lox-1-mediated-hypoxia-induced-pasmcs-proliferation
#6
Wei-Fang Zhang, Tian-Tian Zhu, You-Wen Xiong, Ai-Zhen Xiong, Xiao-Yue Ge, Chang-Ping Hu, Zheng Zhang
BACKGROUND: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressed c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28072480/free-fatty-acids-induce-autophagy-and-lox-1-upregulation-in-cultured-aortic-vascular-smooth-muscle-cells
#7
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Elevation of free fatty acids (FFAs) is known to affect microvascular function and contribute to obesity-associated insulin resistance, hypertension, and microangiopathy. Proliferative and synthetic vascular smooth muscle cells (VSMCs) increase intimal thickness and destabilize atheromatous plaques. This study aimed to investigate whether saturated palmitic acid (PA) and monounsaturated oleic acid (OA) modulate autophagy activity, cell proliferation, and vascular tissue remodeling in an aortic VSMC cell line...
November 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27995732/oxldl-antibody-inhibits-mcp-1-release-in-monocytes-macrophages-by-regulating-ca-2-k-channel-flow
#8
Jinyu Su, Hui Zhou, Xianyan Liu, Jan Nilsson, Gunilla Nordin Fredrikson, Ming Zhao
oxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP-1 release in monocytes/macrophages through their TLR-4 (Toll-like receptor 4) and ERK MAPK pathway and is calcium/potassium channel-dependent. Using blocking antibodies against CD36, TLR-4, SR-AI and LOX-1, only TLR-4 antibody was found to have an inhibitory effect and ERK MAPK-specific inhibitor (PD98059) was found to have a dramatic inhibitory effect compared to inhibitors of other MAPK group members (p38 and JNK MAPKs) on oxLDL-induced MCP-1 release...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27940550/cox-2-dependent-and-independent-effects-of-cox-2-inhibitors-and-nsaids-on-proatherogenic-changes-in-human-monocytes-macrophages
#9
Iryna Voloshyna, Lora J Kasselman, Steven E Carsons, Michael J Littlefield, Irving H Gomolin, Joshua De Leon, Allison B Reiss
It is the second decade of controversy regarding the cardiovascular effects of cyclo-oxygenase-2 (COX-2) inhibitors. At this time, celecoxib is the only available COX-2-specific inhibitor for treatment of pain and inflammation. Therefore, the present study was designed primarily to determine the impact of celecoxib on cholesterol handling (uptake via scavenger receptors and efflux from the cells) and foam cell formation in human THP-1 macrophages, followed by comparison to rofecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs)...
December 9, 2016: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/27891092/dihydrotanshinone-i-attenuates-atherosclerosis-in-apoe-deficient-mice-role-of-nox4-nf-%C3%AE%C2%BAb-mediated-lectin-like-oxidized-ldl-receptor-1-lox-1-of-the-endothelium
#10
Wenwen Zhao, Chunxia Li, Hongwei Gao, Qin Wu, Jingshan Shi, Xiuping Chen
Dihydrotanshinone I (DHT) is a natural compound extracted from Salvia miltiorrhiza Bunge which has been widely used for treating cardiovascular diseases. However, its role in atherosclerosis remains unclear. In this study, the effect of DHT on atherosclerosis were investigated using apolipoprotein E-deficient (ApoE(-/-)) mice and endothelial cells. In lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), DHT (10 nM) decreased lectin-like ox-LDL receptor-1 (LOX-1) and NADPH oxidase 4 (NOX4) expression, reactive oxygen species (ROS) production, NF-κB nuclear translocation, ox-LDL endocytosis and monocytes adhesion...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27866534/-dihydrotestosterone-inhibits-foam-cell-formation-via-a-lectin-like-ox-low-density-lipoprotein-receptor-mediated-mechanism-in-j774-1-cell-line
#11
Y Qiu, H D Hu, B Q Hu, X Y Chen, P Y Xu, L Cui, P Li, C Liu, L Li
Objective: To investigate the effect of dihydrotestosterone (DHT) on lectin-like ox- low-density lipoprotein (LDL) receptor(LOX-1)expression and foam cell formation in the female macrophage cell line J774.1. Methods: In cultured J774.1 cells, after pretreated with DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L, ox-LDL-induced LOX-1 expression and foam cell formation were investigated by quantitative real-time PCR, Western blotting, and oil-red O staining. Results: DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L inhibited ox-LDL-induced LOX-1 mRNA (2...
November 15, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27864235/l5-ldl-from-st-elevation-myocardial-infarction-patients-induces-il-1%C3%AE-production-via-lox-1-and-nlrp3-inflammasome-activation-in-macrophages
#12
Tzu-Ching Yang, Po-Yuan Chang, Shao-Chun Lu
L5-LDL, the most electronegative LDL associated with major cardiovascular risks, significantly rises in patients with ST-segment elevation myocardial infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases has prompted us to investigate whether L5-LDL induces the production of inflammatory cytokines, especially vascular ischemia-related interleukin (IL)-1β in the pathogenesis of STEMI. Clinical data showed that plasma levels of L5-LDL and IL-1β were higher in the STEMI patients than in the controls (p < 0...
November 18, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27825104/human-15-lipoxygenase-1-is-a-regulator-of-dendritic-cell-spreading-and-podosome-formation
#13
Hongya Han, Xiuming Liang, Monica Ekberg, Joanna S Kritikou, Åsa Brunnström, Benjamin Pelcman, Maria Matl, Xinyan Miao, Margareta Andersson, Xiaotian Yuan, Frida Schain, Selina Parvin, Eva Melin, Jan Sjöberg, Dawei Xu, Lisa S Westerberg, Magnus Björkholm, Hans-Erik Claesson
Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of the inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1...
October 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27818578/apoptosis-of-endothelial-cells-by-13-hpode-contributes-to-impairment-of-endothelial-barrier-integrity
#14
Valerie E Ryman, Nandakumar Packiriswamy, Lorraine M Sordillo
Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis of Streptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA) oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1) metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE), can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE), is abundantly produced during vascular activation...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27815075/gly-14-humanin-inhibits-ox-ldl-uptake-and-stimulates-cholesterol-efflux-in-macrophage-derived-foam-cells
#15
Wa-Wa Zhu, Shu-Rong Wang, Zhi-Hua Liu, Yong-Jun Cao, Fen Wang, Jing Wang, Chun-Feng Liu, Ying Xie, Ying Xie, Yan-Lin Zhang
Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264...
January 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27809851/cyclophilin-a-enhances-macrophage-differentiation-and-lipid-uptake-in-high-glucose-conditions-a-cellular-mechanism-for-accelerated-macro-vascular-disease-in-diabetes-mellitus
#16
Surya Ramachandran, Anandan Vinitha, Cheranellore Chandrasekharan Kartha
BACKGROUND: Vascular disease in diabetes is initiated by monocyte adhesion to vascular endothelium, transmigration and formation of foam cells. Increasing clinical evidence supports a role for the secretory protein, cyclophilin A in diabetic vascular disease. The means by which cyclophilin A contributes to vascular lesion development in diabetes is however largely unknown. METHODS: In this study we investigated using THP1 cells and human monocytes whether cyclophilin A under hyperglycemic conditions, functions in the inflammatory cascade as a chemoattractant and increases lipid uptake by formation of foam cells invitro...
3, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27784857/developmental-endothelial-locus-1-del-1-inhibits-oxidized-low-density-lipoprotein-activity-by-direct-binding-and-its-overexpression-attenuates-atherogenesis-in-mice
#17
Akemi Kakino, Yoshiko Fujita, Atsushi Nakano, Sayaka Horiuchi, Tatsuya Sawamura
BACKGROUND: Modified low-density lipoprotein (LDL) binding to scavenger receptors has been implicated in atherosclerosis. It is hypothesized that a third molecule may affect modified LDL binding, therefore, this study focuses on the soluble endogenous protein, developmental endothelial locus-1 (Del-1), as an inhibitor of oxidized LDL (oxLDL) interactions.Methods and Results:Del-1 preferentially bound oxLDL over native LDL in a cell-free binding assay. Del-1 also inhibited DiI-labeled oxLDL uptake by scavenger receptors irrespective of the receptor type (LOX-1, SR-AI, CD36, or SR-BI) expressed in COS-7 cells, and independent of cell type (human coronary artery endothelial cells (HCAECs) or THP-1-derived macrophages)...
November 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27725191/i4-a-synthetic-anti-diabetes-agent-attenuates-atherosclerosis-through-its-lipid-lowering-anti-inflammatory-and-anti-apoptosis-properties
#18
Lingman Ma, Lifen Qian, Qidi Ying, Yan Zhang, Changlin Zhou, Guanzhong Wu
Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE(-/-) mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27712780/carbamylated-low-density-lipoproteins%C3%A2-induce-a-prothrombotic%C3%A2-state%C3%A2-via-lox-1-impact-on-arterial-thrombus-formation-in-vivo
#19
Erik W Holy, Alexander Akhmedov, Thimoteus Speer, Giovanni G Camici, Stephen Zewinger, Nicole Bonetti, Jürg H Beer, Thomas F Lüscher, Felix C Tanner
BACKGROUND: Carbamylation alters low-density lipoprotein (LDL) structure and is thought to promote vascular inflammation and dysfunction in patients with chronic kidney disease (CKD). OBJECTIVES: This study sought to determine whether carbamylated LDL (cLDL) exerts prothrombotic effects in vascular cells and platelets and whether cLDL enhances arterial thrombus formation in vivo. METHODS: LDL was isolated from healthy subjects or patients with CKD by sequential ultracentrifugation...
October 11, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27699091/multimodal-optical-coherence-tomography-and-fluorescence-lifetime-imaging-with-interleaved-excitation-sources-for-simultaneous-endogenous-and-exogenous-fluorescence
#20
Sebina Shrestha, Michael J Serafino, Jesus Rico-Jimenez, Jesung Park, Xi Chen, Siqin Zhaorigetu, Brian L Walton, Javier A Jo, Brian E Applegate
Multimodal imaging probes a variety of tissue properties in a single image acquisition by merging complimentary imaging technologies. Exploiting synergies amongst the data, algorithms can be developed that lead to better tissue characterization than could be accomplished by the constituent imaging modalities taken alone. The combination of optical coherence tomography (OCT) with fluorescence lifetime imaging microscopy (FLIM) provides access to detailed tissue morphology and local biochemistry. The optical system described here merges 1310 nm swept-source OCT with time-domain FLIM having excitation at 355 and 532 nm...
September 1, 2016: Biomedical Optics Express
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