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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 7, 2016: Molecular and Cellular Endocrinology
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
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
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
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
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
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
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
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
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
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...
September 13, 2016: Molecular Medicine Reports
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
Bin Huang, Dae-Weon Park, Suk-Hwan Baek
The activation of toll-like receptor 2 (TLR2) stimulates foam cell formation, which is a key early event in the process of atherosclerosis. In the present study, the role of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) in TLR2-mediated foam cell formation was investigated, and the importance of monocyte chemoattractant protein‑1 (MCP‑1), tissue factor (TF) and lectin‑like oxidized low‑density lipoprotein receptor‑1 (Lox‑1) were examined. Treatment of Raw 264...
October 2016: Molecular Medicine Reports
R R Sharma, O P Awasthi, Kuldeep Kumar
'Kinnow' is a hybrid mandarin, developed at California (USA) but could not become successful there. However, it revolutionized citrus industry in India, Pakistan and Bangladesh. Recent reports indicate that like other citrus fruits, it also suffers from juice-sac granulation but exact cause of this malady is not known. Fully-mature 'Kinnow' fruits were harvested and observations on some physical and biochemical attributes were recorded and their relationship was established with occurrence of granulation. About 12...
March 2016: Journal of Food Science and Technology
G Halac, E Kilic, M A Cikrikcioglu, K Celik, A Toprak-Erek, S Keskin, I Gultepe, R S Celik, N Ozaras, A Yildiz, S Aydin, O Akan, C Karatoprak, Y Sekin, T Asil
OBJECTIVE: The aim of this study was to assess the predisposition for atherosclerosis in patients with RLS through serum sLOX-1 (serum Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1) measurements. BACKGROUND: Recent epidemiological studies have suggested an association of RLS with certain chronic conditions such as diabetes mellitus (DM), obesity, hypertension (HT), and hyperlipidemia. LOX-1 is expressed in endothelial cells, macrophages, and in smooth muscle cells under the effect of proatherogenic conditions...
2016: Bratislavské Lekárske Listy
Monica Bocchia, Sara Galimberti, Lara Aprile, Anna Sicuranza, Antonella Gozzini, Francesca Santilli, Elisabetta Abruzzese, Claudia Baratè, Barbara Scappini, Giulia Fontanelli, Monika Malgorzata Trawinska, Marzia Defina, Alessandro Gozzetti, Alberto Bosi, Mario Petrini, Luca Puccetti
Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1)...
August 5, 2016: Oncotarget
Perla-Monserrat Madrigal-Ruíz, Rosa-Elena Navarro-Hernández, Sandra-Luz Ruíz-Quezada, Fernanda-Isadora Corona-Meraz, Mónica Vázquez-Del Mercado, Eduardo Gómez-Bañuelos, Jorge Castro-Albarran, Flavio Sandoval-García, Luis-Javier Flores-Alvarado, Beatriz-Teresita Martín-Marquez
Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines)...
2016: Journal of Diabetes Research
Mingyi Chen, Hong Qiu, Xin Lin, David Nam, Lucy Ogbu-Nwobodo, Hannah Archibald, Amelia Joslin, Ted Wun, Tatsuya Sawamura, Ralph Green
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL. Increased expression of LOX-1 has been demonstrated in atherosclerotic lesions and diabetic vasculopathy. In this study, we investigate the expression of LOX-1 receptor in sickle cell disease (SCD) vasculopathy. Expression of LOX-1 in brain vascular endothelium is markedly increased and LOX-1 gene expression is upregulated in cultured human brain microvascular endothelial cells by incubation with SCD erythrocytes...
September 2016: Blood Cells, Molecules & Diseases
Ozan Bozkurt, Aykut Kefi, Ömer Demir, Nergis Murat, Sedef Gidener, Ahmet Adil Esen
BACKGROUND/AIM: The aim of this study was to determine the effects of resveratrol on the alterations of cavernosal eNOS and LOX-1 mRNA expression in the hypercholesterolemic condition. MATERIALS AND METHODS: Twenty-one New Zealand white male rabbits were separated into three groups. Rabbits were fed with a normal dietary intake for the control group and a 2% cholesterol diet for the hypercholesterolemia and resveratrol groups for 6 weeks. Resveratrol 4 mg/kg daily was administered for the resveratrol group...
2016: Turkish Journal of Medical Sciences
Nikolaos Eleftheriadis, Hessel Poelman, Niek G J Leus, Birgit Honrath, Constantinos G Neochoritis, Amalia Dolga, Alexander Dömling, Frank J Dekker
The enzyme 15-lipoxygenase-1 (15-LOX-1) plays a dual role in diseases with an inflammatory component. On one hand 15-LOX-1 plays a role in pro-inflammatory gene expression and on the other hand it has been shown to be involved in central nervous system (CNS) disorders by its ability to mediate oxidative stress and damage of mitochondrial membranes under hypoxic conditions. In order to further explore applications in the CNS, novel 15-LOX-1 inhibitors with favorable physicochemical properties need to be developed...
October 21, 2016: European Journal of Medicinal Chemistry
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