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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
Wa-Wa Zhu, Shu-Rong Wang, Zhi-Hua Liu, Yong-Jun Cao, Fen Wang, Jing Wang, Chun-Feng Liu, 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...
November 1, 2016: 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
#7
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...
November 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
#8
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)...
October 26, 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
#9
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...
October 8, 2016: 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
#10
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
#11
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
https://www.readbyqxmd.com/read/27695485/effects-of-porphyromonas-gingivalis-lipopolysaccharide-on-the-expression-of-key-genes-involved-in-cholesterol-metabolism-in-macrophages
#12
Fen Liu, Yi Wang, Jing Xu, Fangqiang Liu, Rongdang Hu, Hui Deng
INTRODUCTION: Cardiovascular diseases are positively correlated with periodontal disease. However, the molecular mechanisms linking atherosclerosis and periodontal infection are not clear. This study aimed to determine whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) altered the expression of genes regulating cholesterol metabolism in macrophages in the presence of low-density lipoprotein (LDL). MATERIAL AND METHODS: THP-1-derived macrophages were exposed to different concentrations (0...
October 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27694040/lox-1-and-tlr4-affect-each-other-and-regulate-the-generation-of-ros-in-a-fumigatus-keratitis
#13
Xinran Gao, Guiqiu Zhao, Cui Li, Jing Lin, Nan Jiang, Qian Wang, Liting Hu, Qiang Xu, Xudong Peng, Kun He, Guoqiang Zhu
PURPOSE: To explore the relationship between LOX-1 and TLR4 in Aspergillus fumigatus (A. fumigatus) keratitis. To determine LOX-1 and TLR4 can affect each other and regulate inflammation through regulation of the generation of reactive oxygen species (ROS) in A. fumigatus keratitis. METHODS: The cornea and abdominal cavity extracted neutrophils of susceptible C57BL/6 mice were infected with A. fumigatus. The cornea and neutrophils were pretreated with LOX-1 neutralizing antibody, Polyinosinic acid (Poly(I)) (the inhibitor of LOX-1) or CLI-095 (the inhibitor of TLR4) separately before infection...
September 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27693798/chronic-lpsf-gq-02-treatment-attenuates-inflammation-and-atherosclerosis-development-in-ldlr-mice
#14
Amanda Karolina Soares E Silva, Fabiana Oliveira Dos Santos Gomes, Bruna Dos Santos Silva, Edlene Lima Ribeiro, Amanda Costa Oliveira, Shyrlene Meyre da Rocha Araújo, Ingrid Tavares de Lima, Anne Gabrielle Vasconcelos Oliveira, Martina Rudnicki, Dulcineia S P Abdalla, Maria do Carmo Alves de Lima, Ivan da Rocha Pitta, Christina Alves Peixoto
BACKGROUND: Atherosclerosis is a complex disorder with a multifactorial pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits hepatic steatosis and inflammation, which are reported as risk factors for atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on atherosclerosis in LDLr-/- mice comparing two treatment periods. METHODS AND RESULTS: LDLr(-/-) mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15 and 30 days, respectively...
September 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27684606/effects-of-cigarette-smoking-on-cardiovascular-related-protein-profiles-in-two-community-based-cohort-studies
#15
Biying Huang, Per Svensson, Johan Ärnlöv, Johan Sundström, Lars Lind, Erik Ingelsson
BACKGROUND AND AIMS: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years)...
September 15, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27672585/the-role-of-lox-1-on-innate-immunity-against-aspergillus-keratitis-in-mice
#16
Kun He, Li-Hui Yue, Gui-Qiu Zhao, Cui Li, Jing Lin, Nan Jiang, Qian Wang, Qiang Xu, Xu-Dong Peng, Li-Ting Hu, Jie Zhang
AIM: To explore the effects of lectin-like ox-LDL receptor (LOX-1) on innate immunity against Aspergillus fumigatus (A. fumigatus ) in mice cornea. METHODS: The mRNA levels of LOX-1 were tested in normal and A. fumigatus infected corneas of C57BL/6 and BALB/c mice. The expression of LOX-1, pro-inflammatory cytokines TNF-α, CXCL1 and IL-6, anti-inflammatory cytokines IL-10, and matrix metalloproteinase 9 (MMP9) were tested with treatment with LOX-1 neutralizing antibody or control IgG in A...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27651806/synthesis-and-evaluation-of-lox-inhibitory-activity-of-2-1-3-dioxo-1h-benzo-de-isoquinolin-2-3h-yl-n-phenylacetamide-derivatives
#17
Ahmad Mohammadi-Farani, Arash Haqiqi, Sahar Jamshidy Navid, Alireza Aliabadi
A family of structurally related LOX enzymes present in human cells which catalyse the metabolism of released arachidonic acid from phospholipids by inflammatory stimuli, to biologically active mediators. Mainly, expression of three types of LOXs occurs in cells, which catalyse the insertion of molecular oxygen into the molecule of arachidonic acid at carbon 5, 12, and 15. According to this chemical reaction, the LOXs are named 5-, 12-, and 15-LOX, amongst which, 15-LOX with isoforms 15-LOX-1 and 15-LOX-2 have critical role in neoplastic diseases...
July 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27647374/human-15-lox-1-active-site-mutations-alter-inhibitor-binding-and-decrease-potency
#18
Michelle Armstrong, Christopher van Hoorebeke, Thomas Horn, Joshua Deschamps, J Cody Freedman, Chakrapani Kalyanaraman, Matthew P Jacobson, Theodore Holman
Human 15-lipoxygenase-1 (h15-LOX-1 or h12/15-LOX) reacts with polyunsaturated fatty acids and produces bioactive lipid derivatives that are implicated in many important human diseases. One such disease is stroke, which is the fifth leading cause of death and the first leading cause of disability in America. The discovery of h15-LOX-1 inhibitors could potentially lead to novel therapeutics in the treatment of stroke, however, little is known about the inhibitor/active site interaction. This study utilizes site-directed mutagenesis, guided in part by molecular modeling, to gain a better structural understanding of inhibitor interactions within the active site...
November 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27633115/mechanism-of-tacrolimus-induced-chronic-renal-fibrosis-following-transplantation-is-regulated-by-ox-ldl-and-its-receptor-lox-1
#19
Shi Deng, Tao Jin, Li Zhang, Hong Bu, Peng Zhang
Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long‑term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK‑52E, were cultured either with oxidized low‑density lipoprotein (ox‑LDL), FK506, ox‑LDL combined with FK506, or vehicle, respectively...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27612308/activity-based-probes-for-15-lipoxygenase-1
#20
Nikolaos Eleftheriadis, Stephanie A Thee, Martijn R H Zwinderman, Niek G J Leus, Frank J Dekker
Human 15-lipoxygenase-1 (15-LOX-1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity-based probes of 15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15-LOX-1 activity-based probe for the efficient activity-based labeling of recombinant 15-LOX-1. 15-LOX-1-dependent labeling in cell lysates and tissue samples was also possible...
September 26, 2016: Angewandte Chemie
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