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Monocyte phospholipase a2

Daniel E Nixon, Ronald J Bosch, Ellen S Chan, Nicholas T Funderburg, Sally Hodder, Jordan E Lake, Michael M Lederman, Karin L Klingman, Judith A Aberg
BACKGROUND: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. OBJECTIVE: To evaluate atorvastatin as a strategy to reduce cardiovascular risk. METHODS: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL...
January 2017: Journal of Clinical Lipidology
Jeanney Lew, Monika Sanghavi, Colby R Ayers, Darren K McGuire, Torbjørn Omland, Dorothee Atzler, Maria O Gore, Ian Neeland, Jarett D Berry, Amit Khera, Anand Rohatgi, James A de Lemos
BACKGROUND: Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology. METHODS: A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study...
February 7, 2017: Circulation
Manjusha Kulkarni, Emily Bowman, Janelle Gabriel, Taylor Amburgy, Elizabeth Mayne, David A Zidar, Courtney Maierhofer, Abigail Norris Turner, Jose A Bazan, Susan L Koletar, Michael M Lederman, Scott F Sieg, Nicholas T Funderburg
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14(+)CD16(-), CD14(+)CD16(+), CD14(Dim)CD16(+)) from HIV negative (HIV(-)) and antiretroviral therapy-treated HIV positive (HIV(+)) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration...
October 2016: Open Forum Infectious Diseases
Corrilynn O Hileman, Vin Tangpricha, Abdus Sattar, Grace A McComsey
OBJECTIVE: Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. DESIGN: SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations...
April 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Christof Ulrich, Bogusz Trojanowicz, Roman Fiedler, Felix Kohler, Anna-Franziska Wolf, Eric Seibert, Matthias Girndt
BACKGROUND: Monocytic products, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), may participate in the development of atherosclerosis. Heterogeneity of monocytes is widely acknowledged. Classical, intermediate, and non-classical subsets can be discerned. Recently, an inflammatory, pro-atherogenic monocyte population could be identified in hemodialysis patients. In this study, we investigated the expression of Lp-PLA2 on leucocytes and different monocyte subpopulations and their possible role in uremia, inflammation, and atherosclerosis...
2017: Nephron
Yu Su, Yingjie Wang, Yue Zhou, Zhenjie Zhu, Qing Zhang, Xuejie Zhang, Wenjuan Wang, Xiaosong Gu, Aisong Guo, Yongjun Wang
Astrocytes, the major glial cell population of the central nervous system (CNS), play important physiological roles related to CNS homeostasis. Growing evidence demonstrates that astrocytes trigger innate immune responses under challenge of a variety of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine mainly secreted from monocytes/macrophages, is involved in inflammation-associated pathophysiology. Here, we displayed that expression of MIF significantly increased following spinal cord injury, in colocalization with microglia and astrocytes...
January 10, 2017: Oncotarget
Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Chithra K Pushpan, Shalini V, Sindhu G, Parvathy Rathnam, Jayalekshmy A, Helen A
Atherosclerosis is a chronic inflammatory disease. The role of inflammation in atherosclerosis is well established, with all stages of disease progression being assessed as inflammatory response to injury. Preventive treatments and drugs identified so far are based on lipid lowering strategies which also involves functional foods and dietary supplementation. The present study investigated the effect of supplementation of Njavara rice bran oil (NjRBO), extracted from a medicinal rice variety, to high cholesterol diet (HCD) fed rats on atherosclerosis by attenuating the inflammatory responses in PBMCs, aortic endothelial cells and macrophages...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jacob Barnes, Valeria Mondelli, Carmine M Pariante
This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2...
January 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Wei Hsum Yap, Nafees Ahmed, Yang Mooi Lim
Maslinic acid is a natural pentacyclic triterpenoid which has anti-inflammatory properties. A recent study showed that secretory phospholipase A2 (sPLA2) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)-sPLA2 is found in human sera and their levels are correlated with severity of inflammation. This study aims to determine whether maslinic acid interacts with hGIIA-sPLA2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA-sPLA2 and inhibited its enzyme activity in a concentration-dependent manner...
October 2016: Lipids
Jie Chen, Hong-wen Cai, Jing Miao, Xiao-ming Xu, Wei Mao
OBJECTIVE: To observe the effects of Danlou Tablet (DT) on inflammatory reaction, and expressions of lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2), and to analyze potential mechanisms. METHODS: Forty male Wistar rats were randomly and equally divided into five groups, i.e., the normal control group, the model group, the Western medicine (WM) group, the low dose DT group, the high dose DT group, 8 in each group. Rats in the normal control group were fed with basic forage for 12 successive weeks, while AS rat model was established in rats of the other four groups by feeding high fat and sugar forage plus intraperitoneal injection of vitamin D₃...
June 2016: Chinese Journal of Integrated Traditional and Western Medicine
Heng Boon Low, Chin Wen Png, Chunwei Li, De Yun Wang, Soon Boon Justin Wong, Yongliang Zhang
The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells...
August 23, 2016: Oncotarget
Markella V Zanni, Mabel Toribio, Gregory K Robbins, Tricia H Burdo, Michael T Lu, Amorina E Ishai, Meghan N Feldpausch, Amanda Martin, Kathy Melbourne, Virginia A Triant, Sujit Suchindran, Hang Lee, Udo Hoffmann, Kenneth C Williams, Ahmed Tawakol, Steven K Grinspoon
IMPORTANCE: Individuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown. OBJECTIVE: To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection. DESIGN, SETTING, PARTICIPANTS: Twelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART)...
July 1, 2016: JAMA Cardiology
Benoit J Arsenault, Payal Kohli, Gilles Lambert, David A DeMicco, Rachel Laskey, Michael M Messig, John J P Kastelein, David D Waters
Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events...
August 15, 2016: American Journal of Cardiology
Laura Pertl, Sabine Kern, Martin Weger, Silke Hausberger, Markus Trieb, Vanessa Gasser-Steiner, Anton Haas, Hubert Scharnagl, Akos Heinemann, Gunther Marsche
PURPOSE: High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients. METHODS: Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients...
2016: PloS One
K Otomo, O Amengual, Y Fujieda, H Nakagawa, M Kato, K Oku, T Horita, S Yasuda, M Matsumoto, K I Nakayama, S Hatakeyama, T Koike, T Atsumi
OBJECTIVE: The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes. METHODS: Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed...
October 2016: Lupus
Munehiro Yamaguchi, Jennifer Zacharia, Tanya M Laidlaw, Barbara Balestrieri
Phospholipases A2 are enzymes that liberate membrane-bound lipids in a tissue and cell-specific fashion. Group V secretory phospholipase A2 is necessary for the development of M2 macrophages and their effector functions in a mouse model of the T-helper-2 allergic airway inflammation. However, the function of group V phospholipase A2 in human M2 activation and T-helper-2 inflammation is ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly identified marker of both human and mouse interleukin-4-activated M2 macrophages and is also found in the lungs of patients with asthma...
July 2016: Journal of Leukocyte Biology
Shiho Kanai, Keiichi Ishihara, Eri Kawashita, Toshiyuki Tomoo, Kazuhiro Nagahira, Yasuhiro Hayashi, Satoshi Akiba
We have previously shown that high-fat cholesterol diet (HFCD)-induced fatty liver and carbon tetrachloride (CCl4)-induced hepatic fibrosis are reduced in mice deficient in group IVA phospholipase A2 (IVA-PLA2), which plays a role in inflammation. We herein demonstrate the beneficial effects of ASB14780 (3-[1-(4-phenoxyphenyl)-3-(2-phenylethyl)-1H-indol-5-yl]propanoic acid 2-amino-2-(hydroxymethyl)propane-1,3-diol salt), an orally active IVA-PLA2 inhibitor, on the development of fatty liver and hepatic fibrosis in mice...
March 2016: Journal of Pharmacology and Experimental Therapeutics
Samuel Hernandez-Anzaldo, Evan Berry, Vesna Brglez, Dickson Leung, Tae Jin Yun, Jun Seong Lee, Janos G Filep, Zamaneh Kassiri, Cheolho Cheong, Gérard Lambeau, Richard Lehner, Carlos Fernandez-Patron
BACKGROUND: Endocrine functions of the heart have been well established. We investigated the hypothesis that cardiac secretion of a unique phospholipase A2 recently identified by our laboratory (cardiac secreted phospholipase A2 [sPLA2]) establishes a heart-liver endocrine axis that is negatively regulated by matrix metalloproteinase-2 (MMP-2). METHODS AND RESULTS: In Mmp2(-/-) mice, cardiac (but not hepatic) sPLA2 was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein-2 and liver X receptor-α pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low-density lipoprotein and in the liver...
November 13, 2015: Journal of the American Heart Association
Yongjun Guo, Bo Li, Xuejing Xu, Rong Wu, Weihua Li
BACKGROUND/AIMS: Group IIA secretory phospholipase A2 (sPLA2-IIA) has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. METHODS: Human aortic smooth muscle cells (HASMCs) were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP). Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL), sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002...
2015: Cellular Physiology and Biochemistry
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