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https://www.readbyqxmd.com/read/28651330/rosiglitazone-improves-insulin-resistance-mediated-by-10-12-conjugated-linoleic-acid-in-a-male-mouse-model-of-metabolic-syndrome
#1
Shari Wang, Leela Goodspeed, Katherine E Turk, Barbara Houston, Laura J den Hartigh
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high fat high sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling PPARγ antagonism. Since thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28645073/analysis-of-ldlr-variants-from-homozygous-fh-patients-carrying-multiple-mutations-in-the-ldlr-gene
#2
Long Jiang, Asier Benito-Vicente, Ling Tang, Aitor Etxebarria, Wei Cui, Kepa B Uribe, Xiao-Dong Pan, Helena Ostolaza, Shi-Wei Yang, Yu-Jie Zhou, Cesar Martin, Lu-Ya Wang
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease with widespread global prevalence that partially accounts for the high prevalence of premature coronary heart disease. Although the majority of research on FH has focused on single heterozygous LDLR mutations, there have been limited reports of double LDLR mutations on the same chromosome. The aim of this study was to gain insight into the clinical consequences of the presence of multiple mutations in the LDLR gene...
June 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28644829/swapping-the-n-and-c-terminal-domains-of-human-apolipoprotein-e3-and-ai-reveals-insights-into-their-structure-activity-relationship
#3
Mark T Lek, Siobanth Cruz, Nnejiuwa U Ibe, Wendy H J Beck, John K Bielicki, Paul M M Weers, Vasanthy Narayanaswami
Apolipoprotein (apo) E3 and apoAI are exchangeable apolipoproteins that play a dominant role in regulating plasma lipoprotein metabolism. ApoE3 (299 residues) is composed of an N-terminal (NT) domain bearing a 4-helix bundle and a C-terminal (CT) domain bearing a series of amphipathic α-helices. ApoAI (243 residues) also comprises a highly helical NT domain and a less structured CT tail. The objective of this study was to understand their structural and functional role by generating domain swapped chimeras: apoE3-NT/apoAI-CT and apoAI-NT/apoE-CT...
2017: PloS One
https://www.readbyqxmd.com/read/28642237/mediator-1-is-atherosclerosis-protective-by-regulating-macrophage-polarization
#4
Liang Bai, Zhao Li, Qianwei Li, Hua Guan, Sihai Zhao, Ruihan Liu, Rong Wang, Jin Zhang, Yuzhi Jia, Jianglin Fan, Nanping Wang, Janardan K Reddy, John Y-J Shyy, Enqi Liu
OBJECTIVE: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated. APPROACH AND RESULTS: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1(ΔMac)/ApoE(-)(/-)) mice and found that atherosclerosis was greater in MED1(ΔMac)/ApoE(-/-) mice than in MED1(fl/fl)/ApoE(-/-) littermates...
June 22, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28638138/immune-regulation-by-oral-tolerance-induces-alternate-activation-of-macrophages-and-reduces-markers-of-plaque-destabilization-in-apob-tm2sgy-ldlr-tm1her-j-mice
#5
Lakshmi Narasimha Thota, Thiruvelselvan Ponnusamy, Sheena Philip, Xinjie Lu, Lakshmi Mundkur
Atherosclerosis is the leading cause for cardiovascular mortality. We determined the effect of multi-antigenic construct expressing three peptides AHC (ApoB100, HSP60 and outer membrane protein of chlamydia pneumonia) in stabilizing advanced atherosclerosis in Apob(tm2Sgy)/Ldlr(tm1Her/J) mice. Atherosclerosis was induced by feeding high fat diet (HFD) to mice for 10 weeks, followed by five oral dosing with purified AHC or ovalbumin on alternate days and continued on HFD for another 10 weeks. Tolerance was associated with significantly higher numbers of regulatory T cells both in aortic sinus and spleen with higher mRNA expression of CTLA4 (3 fold), Foxp3 (1...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637783/paradoxical-suppression-of-atherosclerosis-in-the-absence-of-microrna-146a
#6
Henry S Cheng, Rickvinder Besla, Angela Li, Zhiqi Chen, Eric A Shikatani, Maliheh Nazari-Jahantigh, Adel Hammoutène, My-Anh Nguyen, Michele Geoffrion, Lei Cai, Nadiya Khyzha, Tong Li, Sonya A MacParland, Mansoor Husain, Myron I Cybulsky, Chantal M Boulanger, Ryan E Temel, Andreas Schober, Katey J Rayner, Clinton Robbins, Jason E Fish
Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on pro-inflammatory NF-κB signalling in several cell types, including endothelial cells and bone marrow-derived cells. Importantly, miR-146a expression is elevated in human atherosclerotic plaques, and polymorphisms in the miR-146a pre-cursor have been associated with risk of coronary artery disease. Objective: To define the role of endogenous miR-146a during atherogenesis. Methods and Results: Paradoxically, Low-density lipoprotein receptor (Ldlr)(-/-) mice deficient in miR-146a develop less atherosclerosis, despite having highly elevated levels of circulating pro-inflammatory cytokines...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28631352/overexpressing-stamp2-attenuates-adipose-tissue-angiogenesis-and-insulin-resistance-in-diabetic-apoe-ldlr-mouse-via-a-ppar%C3%AE-cd36-pathway
#7
Feng Wang, Lu Han, Ran-Ran Qin, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Meng-Xiong Tang, Yun Zhang, Ming Zhong, Wei Zhang
The aim of this study was to investigate whether overexpression of STAMP2 improves insulin resistance by regulating angiogenesis in adipose tissues. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Histological and morphological analysis demonstrated that STAMP2 gene overexpression reduced adipocyte size, angiogenesis in epididymal and brown adipose tissues. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited after STAMP2 gene overexpression...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28623937/the-association-of-lipid-metabolism-relative-gene-polymorphisms-and-ischemic-stroke-in-han-and-uighur-population-of-xinjiang
#8
Yun-Hua Yue, Ling-Yun Liu, Liang Hu, You-Mei Li, Jie-Ping Mao, Xiao-Ying Yang, Na-Mu Dila
BACKGROUND: The present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China. METHODS: Four hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes...
June 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#9
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28618417/cholesterol-enhances-colorectal-cancer-progression-via-ros-elevation-and-mapk-signaling-pathway-activation
#10
Caihua Wang, Peiwei Li, Junmei Xuan, Chunpeng Zhu, Jingjing Liu, Lizhen Shan, Qin Du, Yuezhong Ren, Jun Ye
BACKGROUND/AIMS: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. METHODS: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28615463/low-density-lipoprotein-receptor-related-proteins-in-skeletal-development-and-disease
#11
REVIEW
Tao Yang, Bart O Williams
The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28611099/cell-based-bioluminescent-assay-for-monitoring-the-interaction-between-pcsk9-and-the-ldl-receptor
#12
Sarah J Duellman, Thomas Machleidt, James J Cali, Jolanta Vidugiriene
Monitoring the expression of cell-surface receptors, their interaction with extracellular ligands, and their fate upon ligand binding is important for understanding receptor function and developing new therapies. We describe a cell-based method that utilizes bioluminescent protein complementation technology to interrogate binding of a cellular receptor with its extracellular protein ligand, specifically LDLR and PCSK9. Purified, full-length tagged PCSK9 is added to assay wells containing cells that stably express LDLR with an extracellular complementary tag...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28607102/the-dendritic-cell-receptor-dngr-1-promotes-the-development-of-atherosclerosis-in-mice
#13
Yacine Haddad, Charlotte Lahoute, Marc Clément, Ludivine Laurans, Sarvenaz Metghalchi, Lynda Zeboudj, Andreas Giraud, Xavier Loyer, Marie Vandestienne, Julien Wain-Hobson, Bruno Esposito, Stephane Potteaux, Hafid Ait-Oufella, Alain Tedgui, Ziad Mallat, Soraya Taleb
Rationale: Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. However, the molecular links between necrosis and the development of atherosclerosis are not completely understood. C-type lectin receptor (Clec9a) or DNGR1 is preferentially expressed by the CD8α(+) subset of dendritic cells (CD8α(+)DCs) and is involved in sensing necrotic cells. We hypothesized that sensing of necrotic cells by DNGR1 plays a determinant role in the inflammatory response of atherosclerosis...
June 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28600283/inhibition-of-pcsk9-does-not-improve-lipopolysaccharide-induced-mortality-in-mice
#14
Jean-Mathieu Berger, Angel Loza Valdes, Jesper Gromada, Norma Anderson, Jay D Horton
PCSK9 is a secreted protein that targets LDL receptors (LDLR) for degradation in liver. Blocking the interaction of PCSK9 with the LDLR potently reduces plasma LDL-cholesterol levels and cardiovascular events. Recently, it has been suggested that inhibition of PCSK9 might also improve outcomes in mice and humans with sepsis, possibly by increasing LDL receptor (LDLR)-mediated clearance of endotoxins. Sepsis is a complication of a severe microbial infection that has shared pathways with lipid metabolism. Here, we tested whether anti-PCSK9 antibodies prevent death from lipopolysaccharide (LPS)-induced endotoxemia...
June 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28596542/leukocyte-bim-deficiency-does-not-impact-atherogenesis-in-ldlr-mice-despite-a-pronounced-induction-of-autoimmune-inflammation
#15
Lieve Temmerman, Marijke M Westra, Ilze Bot, Bart J M van Vlijmen, Niek Van Bree, Martine Bot, Kim L L Habets, Tom G H Keulers, Johan van der Vlag, Thomas G Cotter, Theo J C van Berkel, Erik A L Biessen
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim (-/-) or wild type bone marrow transplanted ldlr (-/-) mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596373/mitochondrial-oxidative-stress-promotes-atherosclerosis-and-neutrophil-extracellular-traps-in-aged-mice
#16
Ying Wang, Wei Wang, Nan Wang, Alan R Tall, Ira Tabas
RATIONALE: Mitochondrial oxidative stress (mitoOS) has been shown to be increased in various cell types in human atherosclerosis and with aging. However, the role of cell type-specific mitoOS in atherosclerosis in the setting of advanced age and the molecular mechanisms remains to be determined in vivo. OBJECTIVE: The aim of this study was to examine the role of myeloid cell mitoOS in atherosclerosis in aged mice. APPROACH AND RESULTS: Lethally irradiated low-density lipoprotein receptor-deficient mice (Ldlr(-/-) ) were reconstituted with bone marrow from either wild-type or mitochondrial catalase (mCAT) mice...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28595267/cholesterol-uptake-and-regulation-in-high-grade-and-lethal-prostate-cancers
#17
Konrad H Stopsack, Travis A Gerke, Ove Andrén, Swen-Olof Andersson, Edward L Giovannucci, Lorelei A Mucci, Jennifer R Rider
Lethal prostate cancers have higher expression of squalene monooxygenase (SQLE), the second rate-limiting enzyme of cholesterol synthesis. Preclinical studies suggested that aberrant cholesterol regulators, receptors, and transporters contribute to cholesterol accumulation uniformly. We assessed their association with features of aggressive cancers. In the prospective prostate cancer cohorts within the Health Professional Follow-up Study, the Physicians' Health Study, and the Swedish Watchful Waiting Study, tumor mRNA expression profiling was performed...
June 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28592401/transgenic-tomatoes-expressing-the-6f-peptide-and-ezetimibe-prevent-diet-induced-increases-of-interferon-%C3%AE-and-cholesterol-25-hydroxylase-in-jejunum
#18
Pallavi Mukherjee, Greg Hough, Arnab Chattopadhyay, Mohamad Navab, Hannah R Fogelman, David Meriwether, Kevin Williams, Steven Bensinger, Travis Moller, Kym F Faull, Aldons J Lusis, Luisa Iruela-Arispe, Kristina I Bostrom, Peter Tontonoz, Srinivasa T Reddy, Alan M Fogelman
Feeding LDLR-null mice a Western diet (WD) increased the expression of interferon beta (IFN-β) in jejunum as determined by RT-qPCR, immunohistochemistry (IHC), and by ELISA (all p <0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR (p <0.0001), IHC (p = 0.0019), and ELISA (p <0.0001) resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS (p <0.0001). Adding Ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0...
June 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28589929/type-2-innate-lymphoid-cells-control-the-development-of-atherosclerosis-in-mice
#19
Stephen A Newland, Sarajo Mohanta, Marc Clément, Soraya Taleb, Jennifer A Walker, Meritxell Nus, Andrew P Sage, Changjun Yin, Desheng Hu, Lauren L Kitt, Alison J Finigan, Hans-Reimer Rodewald, Christoph J Binder, Andrew N J McKenzie, Andreas J Habenicht, Ziad Mallat
Type-2 innate lymphoid cells (ILC2) are a prominent source of type II cytokines and are found constitutively at mucosal surfaces and in visceral adipose tissue. Despite their role in limiting obesity, how ILC2s respond to high fat feeding is poorly understood, and their direct influence on the development of atherosclerosis has not been explored. Here, we show that ILC2 are present in para-aortic adipose tissue and lymph nodes and display an inflammatory-like phenotype atypical of adipose resident ILC2. High fat feeding alters both the number of ILC2 and their type II cytokine production...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28579235/haematopoietic-tlr4-deletion-attenuates-perivascular-brown-adipose-tissue-inflammation-in-atherosclerotic-mice
#20
Penghao Liu, Gaojian Huang, Zhiyong Cao, Qihai Xie, Tong Wei, Chenglin Huang, Qun Li, Mengwei Sun, Weili Shen, Pingjin Gao
AIMS: To investigate whether haematopoietic TLR4 deletion attenuates perivascular brown adipose tissue inflammation in atherosclerotic mice. METHODS AND RESULTS: Experiments were performed using irradiated LDL receptor-deficient (LDLR(-/-)) mice with marrow from either TLR4-deficient (TLR4(-/-)) or age-matched wild-type (WT) mice. After 12 weeks of being fed a high-cholesterol diet, TLR4(-/-)→LDLR(-/-) mice developed fewer atherosclerotic lesions in the aorta compared to WT→LDLR(-/-) mice...
June 1, 2017: Biochimica et Biophysica Acta
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