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Gene expression profile of human plaque

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https://www.readbyqxmd.com/read/29896299/flow-dependent-epigenetic-regulation-of-igfbp5-expression-by-h3k27me3-contributes-to-endothelial-anti-inflammatory-effects
#1
Suowen Xu, Yanni Xu, Meimei Yin, Shuya Zhang, Peng Liu, Marina Koroleva, Shuyi Si, Peter J Little, Jaroslav Pelisek, Zheng Gen Jin
Rationale : Atherosclerosis is a chronic inflammatory and epigenetic disease that is influenced by different patterns of blood flow. However, the epigenetic mechanism whereby atheroprotective flow controls endothelial gene programming remains elusive. Here, we investigated the possibility that flow alters endothelial gene expression through epigenetic mechanisms. Methods : E n face staining and western blot were used to detect protein expression. Real-time PCR was used to determine relative gene expression...
2018: Theranostics
https://www.readbyqxmd.com/read/29884117/phactr1-splicing-isoforms-and-eqtls-in-atherosclerosis-relevant-human-cells
#2
Valérie-Anne Codina-Fauteux, Mélissa Beaudoin, Simon Lalonde, Ken Sin Lo, Guillaume Lettre
BACKGROUND: Genome-wide association studies (GWAS) have identified a variant (rs9349379) at the phosphatase and actin regulator 1 (PHACTR1) locus that is associated with coronary artery disease (CAD). The same variant is also an expression quantitative trait locus (eQTL) for PHACTR1 in human coronary arteries (hCA). Here, we sought to characterize PHACTR1 splicing pattern in atherosclerosis-relevant human cells. We also explored how rs9349379 modulates the expression of the different PHACTR1 splicing isoforms...
June 8, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29806693/neuronal-calcineurin-transcriptional-targets-parallel-changes-observed-in-alzheimer-disease-brain
#3
Sarah C Hopp, Nathan A Bihlmeyer, John P Corradi, Charles Vanderburg, Angela M Cacace, Sudeshna Das, Timothy W Clark, Rebecca A Betensky, Bradley T Hyman, Eloise Hudry
Synaptic dysfunction and loss are core pathological features in Alzheimer disease (AD). In the vicinity of amyloid-β plaques in animal models, synaptic toxicity occurs and is associated with chronic activation of the phosphatase calcineurin (CN). Indeed, pharmacological inhibition of CN blocks amyloid-β synaptotoxicity. We therefore hypothesized that CN-mediated transcriptional changes may contribute to AD neuropathology and tested this by examining the impact of CN overexpression on neuronal gene expression in vivo...
May 28, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29777114/microrna-expression-profile-of-human-advanced-coronary-atherosclerotic-plaques
#4
Mariana S Parahuleva, Christoph Lipps, Behnoush Parviz, Hans Hölschermann, Bernhard Schieffer, Rainer Schulz, Gerhild Euler
MicroRNA (miR) is reported to be involved in vascular inflammation and may represent a novel class of diagnostic biomarkers in cardiovascular disease. We aimed to identify the miR expression profile in human advanced coronary atherosclerotic plaques (CAP) and to connect this expression to the processes in atherosclerosis. Microarray techniques and TaqMan polymerase chain reaction were used to analyse the global expression of 352 miRs in CAP obtained during ACS MULTI-LINK study. 11 miRs were selected on the basis of their implication in atherosclerosis, endothelial activation, and inflammation...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29692426/transcriptomic-analysis-of-the-liver-of-cholesterol-fed-rabbits-reveals-altered-hepatic-lipid-metabolism-and-inflammatory-response
#5
Weirong Wang, Yulong Chen, Liang Bai, Sihai Zhao, Rong Wang, Baoning Liu, Yali Zhang, Jianglin Fan, Enqi Liu
Rabbits are a suitable animal model for atherosclerosis due to their sensitivity to dietary cholesterol. Moreover, rabbits have lipoprotein profiles that are more similar to humans than those of other laboratory animals. However, little is known about the transcriptomic information related to atherosclerosis in rabbits. We aimed to determine the changes in the livers of rabbits fed a normal chow diet (control) or high cholesterol diet (HCD) by histological examinations and RNA sequencing analysis. Compared with the control group, the lipid levels and small LDL subfractions in plasma were increased, and aortic atherosclerotic plaques were formed in the HCD group...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29518357/elevated-trem2-gene-dosage-reprograms-microglia-responsivity-and-ameliorates-pathological-phenotypes-in-alzheimer-s-disease-models
#6
C Y Daniel Lee, Anthony Daggett, Xiaofeng Gu, Lu-Lin Jiang, Peter Langfelder, Xiaoguang Li, Nan Wang, Yingjun Zhao, Chang Sin Park, Yonatan Cooper, Isabella Ferando, Istvan Mody, Giovanni Coppola, Huaxi Xu, X William Yang
Variants of TREM2 are associated with Alzheimer's disease (AD). To study whether increasing TREM2 gene dosage could modify the disease pathogenesis, we developed BAC transgenic mice expressing human TREM2 (BAC-TREM2) in microglia. We found that elevated TREM2 expression reduced amyloid burden in the 5xFAD mouse model. Transcriptomic profiling demonstrated that increasing TREM2 levels conferred a rescuing effect, which includes dampening the expression of multiple disease-associated microglial genes and augmenting downregulated neuronal genes...
March 7, 2018: Neuron
https://www.readbyqxmd.com/read/29462879/chondrocytes-contribute-to-alphaviral-disease-pathogenesis-as-a-source-of-virus-replication-and-soluble-factor-production
#7
Elisa X Y Lim, Aroon Supramaniam, Hayman Lui, Peta Coles, Wai Suet Lee, Xiang Liu, Penny A Rudd, Lara J Herrero
Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells...
February 15, 2018: Viruses
https://www.readbyqxmd.com/read/29459263/hyperlipidemia-induces-typical-atherosclerosis-development-in-ldlr-and-apoe-deficient-rats
#8
Yongliang Zhao, Yiqing Yang, Roumei Xing, Xueqin Cui, Yufang Xiao, Ling Xie, Panpan You, Tongtong Wang, Li Zeng, Wenhui Peng, Dali Li, Huaqing Chen, Mingyao Liu
BACKGROUND AND AIMS: Low-density lipoprotein receptor (Ldlr) and apolipoprotein E (Apoe) knockout (KO) mice have been widely used as animal models of atherosclerosis. However, data suggested that it is difficult to develop typical atherosclerosis in rats. To this end, Ldlr and Apoe KO rats were generated and the potential to develop novel atherosclerosis models was evaluated. METHODS: We established Apoe/Ldlr single and double KO (DKO) rats via the CRISPR/Cas9 system in the same background...
April 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29353102/aging-african-green-monkeys-manifest-transcriptional-pathological-and-cognitive-hallmarks-of-human-alzheimer-s-disease
#9
Paige E Cramer, Renee C Gentzel, Keith Q Tanis, Joshua Vardigan, Yi Wang, Brett Connolly, Philip Manfre, Kenneth Lodge, John J Renger, Celina Zerbinatti, Jason M Uslaner
While many preclinical models of Alzheimer's disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in 2 higher order species, the African green monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans...
April 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29196460/microglia-in-alzheimer-s-disease
#10
REVIEW
David V Hansen, Jesse E Hanson, Morgan Sheng
Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer's disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to β-amyloid are associated with increased AD risk...
February 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29190775/transcriptome-profiling-analysis-of-senescent-gingival-fibroblasts-in-response-to-fusobacterium-nucleatum-infection
#11
Sun-Hee Ahn, Seongmin Chun, Chungoo Park, Jong-Hee Lee, Seok-Woo Lee, Tae-Hoon Lee
Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum is an important periodontal pathogen involved in the development of bacterial complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the first line of defense against oral microorganisms and locally orchestrate immune responses by triggering the production of reactive oxygen species and pro-inflammatory cytokines (IL-6 and IL-8). The frequency and severity of periodontal diseases is known to increase in elderly subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#12
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
January 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#13
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH 17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28899419/increased-plasma-lipid-levels-exacerbate-muscle-pathology-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy
#14
Nadia Milad, Zoe White, Arash Y Tehrani, Stephanie Sellers, Fabio M V Rossi, Pascal Bernatchez
BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. METHODS: To test the blood vessel contribution to muscle damage in DMD, mdx (4cv) mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets...
September 12, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28668092/dissecting-the-role-of-non-coding-rnas-in-the-accumulation-of-amyloid-and-tau-neuropathologies-in-alzheimer-s-disease
#15
Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H Imboywa, Julie A Schneider, Nathalie Pochet, Anna M Krichevsky, Lori B Chibnik, David A Bennett, Philip L De Jager
BACKGROUND: Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. METHODS: We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging...
July 1, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#16
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II+ microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
July 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28319050/extracellular-matrix-proteomics-identifies-molecular-signature-of-symptomatic-carotid-plaques
#17
Sarah R Langley, Karin Willeit, Athanasios Didangelos, Ljubica Perisic Matic, Philipp Skroblin, Javier Barallobre-Barreiro, Mariette Lengquist, Gregor Rungger, Alexander Kapustin, Ludmilla Kedenko, Chris Molenaar, Ruifang Lu, Temo Barwari, Gonca Suna, Xiaoke Yin, Bernhard Iglseder, Bernhard Paulweber, Peter Willeit, Joseph Shalhoub, Gerard Pasterkamp, Alun H Davies, Claudia Monaco, Ulf Hedin, Catherine M Shanahan, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms. METHODS: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28224128/upregulation-of-th-il-17-pathway-related-genes-in-human-coronary-endothelial-cells-stimulated-with-serum-of-patients-with-acute-coronary-syndromes
#18
Giovanni Cimmino, Loreta Pia Ciuffreda, Giovanni Ciccarelli, Paolo Calabrò, Fiorella Angelica Valeria Ferraiolo, Alessia Rivellino, Raffaele De Palma, Paolo Golino, Francesco Rossi, Plinio Cirillo, Liberato Berrino
BACKGROUND: Inflammation plays an essential role in the development and complications of atherosclerosis plaques, including acute coronary syndromes (ACS). Indeed, previous reports have shown that within the coronary circulation of ACS patients, several soluble mediators are released. Moreover, it has been demonstrated that endothelial dysfunction might play an important role in atherosclerosis as well as ACS pathophysiology. However, the mechanisms by which these soluble mediators might affect endothelial functions are still largely unknown...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28137856/targeting-ire1-with-small-molecules-counteracts-progression-of-atherosclerosis
#19
Ozlem Tufanli, Pelin Telkoparan Akillilar, Diego Acosta-Alvear, Begum Kocaturk, Umut Inci Onat, Syed Muhammad Hamid, Ismail Çimen, Peter Walter, Christian Weber, Ebru Erbay
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#20
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
June 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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