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Peripheral blood gene expression and atherosclerosis

Zhong-Bao Ruan, Xing-Li Fu, Wei Li, Jun Ye, Ru-Zhu Wang, Li Zhu
BACKGROUND: Notch and NF-κB signaling pathways both play important roles in the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF-κB signaling pathways on AS are still unclear. In this study, we aimed to investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF-κB signaling pathways of macrophages in patients with atherosclerosis (AS), so as to seek the treatment of AS from genetic perspective. METHODS: Peripheral blood mononuclears of 31 patients with AS were isolated by density gradient centrifugation and transformed by PMA to macrophages...
September 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
Luran Liu, Yan Liu, Chang Liu, Zhuobo Zhang, Yaojun Du, Hao Zhao
The present study aimed to identify potential biomarkers for atherosclerosis via analysis of gene expression profiles. The microarray dataset no. GSE20129 was downloaded from the Gene Expression Omnibus database. A total of 118 samples from the peripheral blood of female patients was used, including 47 atherosclerotic and 71 non‑atherosclerotic patients. The differentially expressed genes (DEGs) in the atherosclerosis samples were identified using the Limma package. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery tool...
October 2016: Molecular Medicine Reports
Dan Li, Yajin Liu, Xu Zhang, Huizhen Lv, Wei Pang, Xiaoli Sun, Li-Ming Gan, Bruce D Hammock, Ding Ai, Yi Zhu
RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition in atherogenesis. METHODS AND RESULTS: Mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double-knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce arteriosclerosis...
September 2016: Journal of Molecular and Cellular Cardiology
Robert C Grenn, Srilakshmi Yalavarthi, Alex A Gandhi, Nayef M Kazzaz, Carlos Núñez-Álvarez, Diego Hernández-Ramírez, Antonio R Cabral, W Joseph McCune, Paula L Bockenstedt, Jason S Knight
OBJECTIVES: Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS...
July 18, 2016: Annals of the Rheumatic Diseases
Yaowapa Maneerat, Kriengchai Prasongsukarn, Surachet Benjathummarak, Wilanee Dechkhajorn, Urai Chaisri
BACKGROUND: Atherosclerosis is a multifactorial disorder of the heart vessels that develops over decades, coupling inflammatory mechanisms and elevated total cholesterol levels under the influence of genetic and environmental factors. Without effective intervention, atherosclerosis consequently causes coronary heart disease (CHD), which leads to increased risk of sudden death. Polymorphonuclear neutrophils play a pivotal role in inflammation and atherogenesis. Human neutrophil peptides (HNPs) or alpha (α)-defensins are cysteine-rich cation polypeptides that are produced and released from activated polymorphonuclear neutrophil granules during septic inflammation and acute coronary vascular disorders...
2016: Lipids in Health and Disease
X Feng, W Chen, L Xiao, F Gu, J Huang, B P Tsao, L Sun
OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a key regulator of both atherosclerosis and systemic lupus erythematosus (SLE), yet factors leading to its overproduction remain unclear. To explore regulation of MIF in SLE, we studied effects and potential mechanisms of type I interferon (IFN) and artesunate (ART), an antimalarial agent extracted from Chinese herbs, on levels of MIF. METHODS: Serum and peripheral blood cells from SLE patients and healthy controls were measured for MIF levels by ELISA and type I IFN-inducible gene expressions by real-time PCR, respectively, and assessed for associations by Spearman correlation...
May 26, 2016: Lupus
Sheng-Chao Ma, Hui-Ping Zhang, Fan-Qi Kong, Hui Zhang, Cheng Yang, Yang-Yang He, Yan-Hua Wang, An-Ning Yang, Ju Tian, Xiao-Ling Yang, Ming-Hao Zhang, Hua Xu, Yi-Deng Jiang, Zheng Yu
The aim of the present study was to identify an effective method for detecting early‑phase atherosclerosis (AS), as well as to provide useful DNA methylation profiles to serve as biomarkers for the detection of AS. A total of 300 individuals (150 AS patients and 150 healthy subjects) were recruited for peripheral blood DNA methylation analyses at 12 gene promoter loci using nested methylation‑specific polymerase chain reaction in a test set. Based on the test set, the promoter methylation of TIMP metallopeptidase inhibitor 1 (TIMP1), ATP binding cassette subfamily A member 1 (ABCA1), and acetyl-CoA acetyltransferase 1 (ACAT1) were determined to be candidate biomarkers; demonstrating the highest sensitivity (88%) and specificity (90%)...
June 2016: Molecular Medicine Reports
Samaneh Enayati, Soroush Seifirad, Parvin Amiri, Milad Abolhalaj, Mahsa Mohammad-Amoli
BACKGROUND: Several inflammatory mediators have been proposed to contribute to the pathogenesis of atherosclerosis. The aim of this study was to evaluate the quantitative expression of pro-inflammatory cytokines in un-stimulated peripheral blood mononuclear cell of patients with coronary artery disease (CAD). METHODS: Interleukin-1 beta (IL-1β), tumor necrosis factor-alpha, and interferon-gamma (IFN-γ) gene expression were evaluated in angiography confirmed patients with and without CAD in a case-control study using quantitative real-time polymerase chain reaction...
September 2015: ARYA Atherosclerosis
Chaojun Chen, Qiang Fu, Yuejun Li, Zhiliang Li
OBJECTIVE: To investigate the anti-atherosclerosis mechanism of Astragalus mongholicus polysaccharides (APS) by examining its effect on gene expression profiles of the dendritic cells (DCs) from healthy donors. METHODS: Peripheral blood DCs from healthy donors were incubated with 200 mg/L APS overnight, and changes in the gene expression profiles were investigated using microarray technique and RT-PCR. RESULTS: Compared with the control cells, APS-treated DCs showed significantly up-regulated expressions of CD36 (0...
December 2015: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Martin Kächele, Anita M Hennige, Jürgen Machann, Anja Hieronimus, Apostolia Lamprinou, Fausto Machicao, Fritz Schick, Andreas Fritsche, Norbert Stefan, Bernd Nürnberg, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Phosphoinositide 3-kinase γ (PI3Kγ) is a G-protein-coupled receptor-activated lipid kinase mainly expressed in leukocytes and cells of the cardiovascular system. PI3Kγ plays an important signaling role in inflammatory processes. Since subclinical inflammation is a hallmark of atherosclerosis, obesity-related insulin resistance, and pancreatic β-cell failure, we asked whether common genetic variation in the PI3Kγ gene (PIK3CG) contributes to body fat content/distribution, serum adipokine/cytokine concentrations, alterations in plasma lipid profiles, insulin sensitivity, insulin release, and glucose homeostasis...
2015: PloS One
Vsevolod Y Polotsky, Shannon Bevans-Fonti, Dmitry N Grigoryev, Naresh M Punjabi
Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures...
2015: PloS One
L Perisic, S Aldi, Y Sun, L Folkersen, A Razuvaev, J Roy, M Lengquist, S Åkesson, C E Wheelock, L Maegdefessel, A Gabrielsen, J Odeberg, G K Hansson, G Paulsson-Berne, U Hedin
BACKGROUND: Embolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability. METHODS: Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed...
March 2016: Journal of Internal Medicine
C Y Zhang, B Qu, P Ye, J Li, C D Bao
This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses...
2015: Genetics and Molecular Research: GMR
Xiaoyu Wu, Maani Hakimi, Markus Wortmann, Jian Zhang, Dittmar Böckler, Susanne Dihlmann
BACKGROUND: Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age. FINDINGS: Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0...
2015: Immunity & Ageing: I & A
Sihui Li, Qian Fan, Shaolin He, Tingting Tang, Yuhua Liao, Jiangjiao Xie
BACKGROUND: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. AIMS: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD)...
2015: Cellular Physiology and Biochemistry
Wenwen Yan, Lemin Wang, Jinfa Jiang, Wenjun Xu, Zhu Gong, Qianglin Duan, Chuanrong Li, Haoming Song, Lin Che, Yuqin Shen, Lin Zhou
OBJECTIVE: To identify differentially expressed T cells-related genes in peripheral blood mononuclear cells and compare their differences in T cell activation and subset functions in different stages of coronary atherosclerosis disease (CAD). METHODS: 20 patients with acute myocardial infarction patients (AMI), 20 patients with stable angina pectoris (SA) and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the expression of T cell related genes among three groups...
2015: International Journal of Clinical and Experimental Medicine
Andrew T Hale, Chris T Longenecker, Ying Jiang, Sara M Debanne, Danielle E Labatto, Norma Storer, Anne Hamik, Grace A McComsey
OBJECTIVE: To determine the relationships between Krüppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART). DESIGN: Double-blind, randomized, placebo-controlled trial. METHODS: We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo...
August 24, 2015: AIDS
Li-Pang Chuang, Ning-Hung Chen, Yuling Lin, Wen-Shan Ko, Jong-Hwei S Pang
PURPOSE: Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. Monocyte chemoattractant protein-1 (MCP-1), as a critical factor for monocyte infiltration, is known to play a role in the development of atherosclerosis. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the MCP-1 expression of monocytes. METHODS: Peripheral blood was sampled from 61 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of MCP-1...
March 2016: Sleep & Breathing, Schlaf & Atmung
Hsiao-Huei Chen, Kianoosh Keyhanian, Xun Zhou, Ragnar O Vilmundarson, Naif A M Almontashiri, Shelly A Cruz, Nihar R Pandey, Nida Lerma Yap, Tiffany Ho, Chloe A Stewart, Hua Huang, Aswin Hari, Michele Geoffrion, Ruth McPherson, Katey J Rayner, Alexandre F R Stewart
RATIONALE: Inflammation impairs macrophage cholesterol clearance from vascular tissues and promotes atherosclerosis. Inflammatory macrophages suppress expression of the transcription cofactor interferon regulatory factor 2-binding protein 2 (IRF2BP2), and genetic variants near IRF2BP2 associate with ischemic heart disease progression in humans. OBJECTIVES: To test whether IRF2BP2 in macrophages affects atherosclerosis in mice and humans. METHODS AND RESULTS: We generated mice that delete IRF2BP2 in macrophages...
September 25, 2015: Circulation Research
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