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Atheroprotective gene expression

Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Yixi Chen, Jianping Cao, Qihui Zhao, Haiyong Luo, Yiguang Wang, Wenjian Dai
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content...
March 2018: Korean Journal of Physiology & Pharmacology
Olivia A Attallah, W K B Khalil, Mohamed M S Abdel Mottaleb, E Girgis
In our present work some biological tests were carried out to assess the biocompatibility of nicotinic acid coated magnetite nanorods. Pure and coated nanorods were injected intraperitoneally to cholesterol fed mice with dose values of 25, 50 mg/Kg. Investigations were done on treated mice with/without exposure to low frequency electromagnetic field (EMF) and samples were collected fourteen days post treatment. Toxicological effects were evaluated using Micronucleus and DNA fragmentation analysis. The results indicated that low dose (25 mg/Kg) nicotinic acid coated nanorods had insignificant toxicological effects in comparison to that of control group...
February 1, 2018: Journal of Nanoscience and Nanotechnology
Victor Brito, Katia Mellal, Karina F Zoccal, Yosdel Soto, Liliane Ménard, Roger Sarduy, Lucia H Faccioli, Huy Ong, Ana M Vázquez, Sylvie Marleau
The retention of lipoprotein particles in the intima, in particular to glycosaminoglycan side chains of proteoglycans, is a critical step in atherosclerosis initiation. Administration of chP3R99, a chimeric mouse/human monoclonal antibody inducing an anti-idiotypic network response against glycosaminoglycans was previously shown to prevent atherosclerotic lesion progression, yet its effect in the late-stage progression of lesions remains unknown. This study investigated the effect of chP3R99 at a late stage of disease development in apolipoprotein E-deficient mice and the vascular mechanisms involved...
2017: Frontiers in Pharmacology
Julia J Mack, Thiago S Mosqueiro, Brian J Archer, William M Jones, Hannah Sunshine, Guido C Faas, Anais Briot, Raquel L Aragón, Trent Su, Milagros C Romay, Austin I McDonald, Cheng-Hsiang Kuo, Carlos O Lizama, Timothy F Lane, Ann C Zovein, Yun Fang, Elizabeth J Tarling, Thomas Q de Aguiar Vallim, Mohamad Navab, Alan M Fogelman, Louis S Bouchard, M Luisa Iruela-Arispe
Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation...
November 20, 2017: Nature Communications
Mizanur Rahman, Johnny Steuer, Peter Gillgren, Assim Hayderi, Anquan Liu, Johan Frostegård
BACKGROUND: Atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (DCs) and T cells, dead cells, and oxidized low-density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. METHODS AND RESULTS: Human DCs differentiated from peripheral blood monocytes were treated with human HSP60 or HSP90 and autologous T cells were cocultured with these pretreated DCs (mDCs)...
November 18, 2017: Journal of the American Heart Association
Ei Christodoulou, N P E Kadoglou, M Stasinopoulou, O A Konstandi, C Kenoutis, Z I Kakazanis, A Rizakou, N Kostomitsopoulos, G Valsami
BACKGROUND AND AIMS: We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE(-/-)) mice. METHODS: Fifty male, ApoE(-/-) mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks)...
November 1, 2017: Atherosclerosis
Nassim E Ajami, Shakti Gupta, Mano R Maurya, Phu Nguyen, Julie Yi-Shuan Li, John Y-J Shyy, Zhen Chen, Shu Chien, Shankar Subramaniam
Blood flow and vascular shear stress patterns play a significant role in inducing and modulating physiological responses of endothelial cells (ECs). Pulsatile shear (PS) is associated with an atheroprotective endothelial phenotype, while oscillatory shear (OS) is associated with an atheroprone endothelial phenotype. Although mechanisms of endothelial shear response have been extensively studied, most studies focus on characterization of single molecular pathways, mainly at fixed time points after stress application...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
Alexandros Nicolaou, Bernd H Northoff, Kristina Sass, Jana Ernst, Alexander Kohlmaier, Knut Krohn, Christian Wolfrum, Daniel Teupser, Lesca M Holdt
BACKGROUND AND AIMS: In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mice on the LDL-receptor deficient (Ldlr(-/-)) background. It was the aim of the current study to identify causative genes at this locus. METHODS: We established a congenic mouse model, where FVB.Chr3(B6/B6) mice carried an 80 Mb interval of distal Chr3 on an otherwise FVB...
September 4, 2017: Atherosclerosis
Keith A Bailey, Fawaz G Haj, Scott I Simon, Anthony G Passerini
Atherosclerosis impacts arteries where disturbed blood flow renders the endothelium susceptible to inflammation. Cytokine activation of endothelial cells (EC) upregulates VCAM-1 receptors that target monocyte recruitment to atherosusceptible regions. Endoplasmic reticulum (ER) stress elicits EC dysregulation in metabolic syndrome. We hypothesized that ER plays a central role in mechanosensing of atherosusceptible shear stress (SS) by signaling enhanced inflammation. Aortic EC were stimulated with low-dose TNFα (0...
August 15, 2017: Scientific Reports
Zhao Li, Marcy Martin, Jin Zhang, Hsi-Yuan Huang, Liang Bai, Jiao Zhang, Jian Kang, Ming He, Jie Li, Mano R Maurya, Shakti Gupta, Guangjin Zhou, Panjamaporn Sangwung, Yong-Jiang Xu, Ting Lei, Hsien-Da Huang, Mohit Jain, Mukesh K Jain, Shankar Subramaniam, John Y-J Shyy
BACKGROUND: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages...
October 3, 2017: Circulation
Yajin Liu, Xuan Fang, Xu Zhang, Jing Huang, Jinlong He, Liyuan Peng, Chenji Ye, Yingmei Wang, Fengxia Xue, Ding Ai, Dan Li, Yi Zhu
BACKGROUND AND PURPOSE: Atherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. ω-3 polyunsaturated fatty acids (ω-3) have protective effects in atherosclerosis; however, the molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω-3 and investigate the underlying mechanisms. EXPERIMENTAL APPROACH: We evaluated the development of atherosclerosis in LDL-receptor-deficient mice (LDLR(-/-) ) fed a Western-type diet (WTD) plus ω-3 and also LDLR(-/-) and fat-1 transgenic (LDLR(-/-) -fat-1(tg) ) mice fed a WTD...
August 3, 2017: British Journal of Pharmacology
Dong Ju Son, Yu Yeon Jung, Young Sik Seo, Heonyong Park, Dong Hun Lee, Sanghyeon Kim, Yoon-Seok Roh, Sang Bae Han, Do Young Yoon, Jin Tae Hong
Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied. Methods: IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively...
2017: Theranostics
Sufang Li, Chengfu Cao, Hong Chen, Junxian Song, Chongyou Lee, Jing Zhang, Feng Zhang, Qiang Geng, Zheng Li, Jingjin Li
Experimental studies have demonstrated several effects of statins in acute coronary syndrome (ACS) that may extend their clinical benefit beyond the lipid profile modification itself. However, the precise underlying mechanism remains to be elucidated. microRNAs (miRNAs) serve significant roles in the pathophysiology of atherosclerotic plaque progression. The present study investigated the protective role of statins in patients with unstable angina (UA) by regulating the circulating miRNA network. miRNA array results demonstrated that there were 21 differentially expressed miRNAs in non‑statin‑treated patients with UA (n=8) compared with non‑coronary artery disease controls (n=8), and 33 differentially expressed miRNAs in statin‑treated patients with UA (n=8) compared with non‑statin patients...
July 2017: Molecular Medicine Reports
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Shyy, Shu Chien
The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells...
July 1, 2017: Physiological Genomics
Shanshan Cui, Wen Li, Xin Lv, Pengyan Wang, Yuxia Gao, Guowei Huang
The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells...
May 5, 2017: International Journal of Molecular Sciences
Yao Wei Lu, Anthony M Lowery, Li-Yan Sun, Harold A Singer, Guohao Dai, Alejandro P Adam, Peter A Vincent, John J Schwarz
OBJECTIVE: Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo. APPROACH AND RESULTS: To study endothelial Mef2c, we generated endothelial-specific deletion of Mef2c using Tie2-Cre or Cdh5-Cre-ER(T2) and examined aortas and carotid arteries by en face immunofluorescence. We observed enhanced actin stress fiber formation in the Mef2c-deleted thoracic aortic endothelium (laminar flow region), similar to those observed in normal aortic inner curvature (disturbed flow region)...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Yvonne Döring, Heidi Noels, Emiel P C van der Vorst, Carlos Neideck, Virginia Egea, Maik Drechsler, Manuela Mandl, Lukas Pawig, Yvonne Jansen, Katrin Schröder, Kiril Bidzhekov, Remco T A Megens, Wendy Theelen, Barbara M Klinkhammer, Peter Boor, Leon Schurgers, Rick van Gorp, Christian Ries, Pascal J H Kusters, Allard van der Wal, Tilman M Hackeng, Gabor Gäbel, Ralf P Brandes, Oliver Soehnlein, Esther Lutgens, Dietmar Vestweber, Daniel Teupser, Lesca M Holdt, Daniel J Rader, Danish Saleheen, Christian Weber
BACKGROUND: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, in particular, because the somatic deletion of the CXCR4 gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection...
July 25, 2017: Circulation
Sindy Giebe, Natalia Cockcroft, Katherine Hewitt, Melanie Brux, Anja Hofmann, Henning Morawietz, Coy Brunssen
Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq)...
August 2017: Redox Biology
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