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Gene expression in atherosclerotic plaque culture

B Li, X Y Li, W Zhong, C Shao, Z Q Wang, W Yuan, J C Yan
Objective: To explore whether CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells (VSMCs) could influence the formation of atherosclerotic calcification. Methods: Fifteen 8-week-old male ApoE(-/-)(C57BL/6J-KO) mice fed with high fat diet for 5 weeks were randomly divided into three groups by using stochastic indicator method as follows: control group, n=5; agonist-CD137 group: agonist-CD137 antibody 200 μg/2 weeks for 4 weeks, ip, n=5; anti-CD137 group: 200 μg anti-CD137 antibody+ 200 μg agonist-CD137 antibody/2 weeks for 4 weeks, ip, n=5...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
Shaomin Qian, Jenna N Regan, Maxwell T Shelton, April Hoggatt, Khalid S Mohammad, Paul B Herring, Cheikh I Seye
BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE(-/-)P2Y2R(-/-)) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo...
December 15, 2016: Atherosclerosis
Glykeria Karadimou, Lasse Folkersen, Martin Berg, Ljubica Perisic, Andrea Discacciati, Joy Roy, Göran K Hansson, Jonas Persson, Gabrielle Paulsson-Berne
AIMS: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n = 123)...
January 2017: Cardiovascular Research
Yingling Xu, Ji Zhu, Xiao Hu, Cui Wang, Dezhao Lu, Chenxue Gong, Jinhuan Yang, Lei Zong
Endothelial dysfunction, which includes endothelial oxidative damage and vascular inflammation, is a key initiating step in the pathogenesis of atherosclerosis (AS) and an independent risk factor for this disorder. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation. In this study, we hypothesize that CLIC1 plays an important role in AS. Apolipoprotein E-deficient mice were supplied with a normal diet or a high-fat and high-cholesterol diet for 8 weeks...
2016: PloS One
Kristiina Rajamäki, Mikko I Mäyränpää, Ana Risco, Jarno Tuimala, Katariina Nurmi, Ana Cuenda, Kari K Eklund, Katariina Öörni, Petri T Kovanen
OBJECTIVE: Activation of the inflammasome pathway in macrophages results in the secretion of 2 potent proinflammatory and proatherogenic cytokines, interleukin (IL)-1β, and IL-18. Atherosclerotic lesions are characterized by the presence of various endogenous activators of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, including cholesterol crystals and extracellular ATP. The aim of this study was to comprehensively characterize the expression of inflammasome pathway components and regulators in human atherosclerotic lesions...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Jing-Jing Yang, Peng Li, Fu Wang, Wen-Jing Liang, Hui Ma, Yuan Chen, Zhi-Min Ma, Quan-Zhong Li, Qi-Sheng Peng, Yun Zhang, Shuang-Xi Wang
AIMS: Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. METHODS AND RESULTS: In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement...
August 16, 2016: Oncotarget
Wei Yang, Fu Liang Ng, Kenneth Chan, Xiangyuan Pu, Robin N Poston, Meixia Ren, Weiwei An, Ruoxin Zhang, Jingchun Wu, Shunying Yan, Haiteng Situ, Xinjie He, Yequn Chen, Xuerui Tan, Qingzhong Xiao, Arthur T Tucker, Mark J Caulfield, Shu Ye
Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A...
July 2016: PLoS Genetics
Wei Xie, Liang Li, Min Zhang, Hai-Peng Cheng, Duo Gong, Yun-Cheng Lv, Feng Yao, Ping-Ping He, Xin-Ping Ouyang, Gang Lan, Dan Liu, Zhen-Wang Zhao, Yu-Lin Tan, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
Atherosclerotic lesions are lipometabolic disorder characterized by chronic progressive inflammation in arterial walls. Previous studies have shown that macrophage-derived lipoprotein lipase (LPL) might be a key factor that promotes atherosclerosis by accelerating lipid accumulation and proinflammatory cytokine secretion. Increasing evidence indicates that microRNA-27 (miR-27) has beneficial effects on lipid metabolism and inflammatory response. However, it has not been fully understood whether miR-27 affects the expression of LPL and subsequent development of atherosclerosis in apolipoprotein E knockout (apoE KO) mice...
2016: PloS One
Monica Madalina Tucureanu, Elena Butoi, Ana-Maria Gan, Daniela Stan, Cristina Ana Constantinescu, Manuela Calin, Maya Simionescu, Ileana Manduteanu
In atherosclerotic plaques, macrophages (MAC) and smooth muscle cells (SMC) frequently reside in close proximity and resistin (Rs) and fractalkine (Fk) are present at increased levels, resistin being associated with CD68 macrophages and fractalkine predominantly associated with intimal SMC; however, their role in this location is not clear, yet. The objective of this study was to determine whether the cross-talk between MAC-SMC induces changes in MAC cytokine phenotype and if Fk and Rs have a role in the process...
July 2016: Cytokine
Yusuke Higashi, Sergiy Sukhanov, Shaw-Yung Shai, Svitlana Danchuk, Richard Tang, Patricia Snarski, Zhaohui Li, Patricia Lobelle-Rich, Meifang Wang, Derek Wang, Hong Yu, Ronald Korthuis, Patrice Delafontaine
BACKGROUND: We have previously shown that systemic infusion of insulin-like growth factor-1 (IGF-1) exerts anti-inflammatory and antioxidant effects and reduces atherosclerotic burden in apolipoprotein E (Apoe)-deficient mice. Monocytes/macrophages express high levels of IGF-1 receptor (IGF1R) and play a pivotal role in atherogenesis, but the potential effects of IGF-1 on their function are unknown. METHODS AND RESULTS: To determine mechanisms whereby IGF-1 reduces atherosclerosis and to explore the potential involvement of monocytes/macrophages, we created monocyte/macrophage-specific IGF1R knockout (MΦ-IGF1R-KO) mice on an Apoe(-/-) background...
June 7, 2016: Circulation
Tobias Asdonk, Martin Steinmetz, Alexander Krogmann, Christine Ströcker, Catharina Lahrmann, Inga Motz, Kathrin Paul-Krahe, Anna Flender, Theresa Schmitz, Winfried Barchet, Gunther Hartmann, Georg Nickenig, Sebastian Zimmer
Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA-5) belongs to the intracellular retinoic acid inducible gene-I like receptors and its activation promotes pro-inflammatory mechanisms. Here, we studied the effect of MDA-5 stimulation in vascular biology. To gain insights into MDA-5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA-5 agonist polyIC (long double-stranded RNA)...
September 2016: Journal of Cellular and Molecular Medicine
Masato Furuhashi, Takahiro Fuseya, Masaki Murata, Kyoko Hoshina, Shutaro Ishimura, Tomohiro Mita, Yuki Watanabe, Akina Omori, Megumi Matsumoto, Takeshi Sugaya, Tsuyoshi Oikawa, Junichi Nishida, Nobuaki Kokubu, Marenao Tanaka, Norihito Moniwa, Hideaki Yoshida, Norimasa Sawada, Kazuaki Shimamoto, Tetsuji Miura
OBJECTIVE: Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes and macrophages, and elevated circulating FABP4 level is associated with obesity-mediated metabolic phenotype. We systematically investigated roles of FABP4 in the development of coronary artery atherosclerosis. APPROACH AND RESULTS: First, by immunohistochemical analyses, we found that FABP4 was expressed in macrophages within coronary atherosclerotic plaques and epicardial/perivascular fat in autopsy cases and macrophages within thrombi covering ruptured coronary plaques in thrombectomy samples from patients with acute myocardial infarction...
May 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
N G Nikiforov, V J Makeev, N V Elizova, A N Orekhov
Monocytes were isolated from blood of patients belonging to three groups: those with normal intima-media thickness (IMT) of carotid arteries, patients with increased IMT and patients with atherosclerotic plaques. The degree of activation of the macrophages was determined by the concentration of the cytokine TNF-α and chemokine CCL18 in the culture medium. When comparing the average values of the concentrations of TNF-α and CCL18 for patients in all groups dramatic individual differences were revealed. These individual differences were found within each group and in the pool...
July 2015: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
Aleksandra Leszczynska, Aideen O'Doherty, Eric Farrell, Jana Pindjakova, Fergal J O'Brien, Timothy O'Brien, Frank Barry, Mary Murphy
The cellular and molecular basis of vascular calcification (VC) in atherosclerosis is not fully understood. Here, we investigate role of resident/circulating progenitor cells in VC and contribution of inflammatory plaque environment to this process. Vessel-derived stem/progenitor cells (VSCs) and mesenchymal stem cells (MSCs) isolated from atherosclerotic ApoE(-/-) mice showed significantly more in vitro osteogenesis and chondrogenesis than cells generated from control C57BL/6 mice. To assess their ability to form bone in vivo, cells were primed chondrogenically or cultured in control medium on collagen glycosaminoglycan scaffolds in vitro prior to subcutaneous implantation in ApoE(-/-) and C57BL/6 mice using a crossover study design...
April 2016: Stem Cells
Joshua A Dubland, Gordon A Francis
PURPOSE OF REVIEW: Smooth muscle cells (SMCs) form the thickened intimal layer in atherosclerosis-prone arteries in early life, and provide the initial site for retention and uptake of atherogenic lipoproteins. Here we review current knowledge regarding the importance of SMCs in the deposition of cholesterol in atherosclerotic plaque. RECENT FINDINGS: SMCs were found to comprise at least 50% of total foam cells in human coronary artery atherosclerosis, and exhibit a selective loss of expression of the cholesterol efflux promoter ATP-binding cassette transporter A1...
April 2016: Current Opinion in Lipidology
Li-Hao Huang, Elaina M Melton, Haibo Li, Paul Sohn, Maximillian A Rogers, Mary Jo Mulligan-Kehoe, Steven N Fiering, William F Hickey, Catherine C Y Chang, Ta-Yuan Chang
Acyl-CoA:cholesterol acyltransferase 1 (Acat1) converts cellular cholesterol to cholesteryl esters and is considered a drug target for treating atherosclerosis. However, in mouse models for atherosclerosis, global Acat1 knockout (Acat1(-/-)) did not prevent lesion development. Acat1(-/-) increased apoptosis within lesions and led to several additional undesirable phenotypes, including hair loss, dry eye, leukocytosis, xanthomatosis, and a reduced life span. To determine the roles of Acat1 in monocytes/macrophages in atherosclerosis, we produced a myeloid-specific Acat1 knockout (Acat1(-M/-M)) mouse and showed that, in the Apoe knockout (Apoe(-/-)) mouse model for atherosclerosis, Acat1(-M/-M) decreased the plaque area and reduced lesion size without causing leukocytosis, dry eye, hair loss, or a reduced life span...
March 18, 2016: Journal of Biological Chemistry
Rachel J Roth Flach, Athanasia Skoura, Anouch Matevossian, Laura V Danai, Wei Zheng, Christian Cortes, Samit K Bhattacharya, Myriam Aouadi, Nana Hagan, Joseph C Yawe, Pranitha Vangala, Lorena Garcia Menendez, Marcus P Cooper, Timothy P Fitzgibbons, Leonard Buckbinder, Michael P Czech
Signalling pathways that control endothelial cell (EC) permeability, leukocyte adhesion and inflammation are pivotal for atherosclerosis initiation and progression. Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans. On the basis of endothelial-specific MAP4K4 gene silencing and gene ablation experiments in Apoe(-/-) mice, we show that MAP4K4 in ECs markedly promotes Western diet-induced aortic macrophage accumulation and atherosclerotic plaque development...
December 21, 2015: Nature Communications
Hao Yan, Ying Ma, Yan Li, Xiaohui Zheng, Ping Lv, Yuan Zhang, Jia Li, Meijuan Ma, Le Zhang, Congye Li, Rongqing Zhang, Feng Gao, Haichang Wang, Ling Tao
Toll-like receptor (TLR) 4 induced inflammation was reported to play an important role in atherosclerotic plaque stability. Recent studies indicated that insulin could inhibit inflammation by activating phosphatidylinositol 3-kinase-Akt-dependent (PI3K-Akt) signaling pathway. In the current study, we hypothesized that insulin would inhibit TLR4 induced inflammation via promoting PI3K-Akt activation, thus enhancing the stabilization of atherosclerotic plaques. In order to mimic the process of plaque formation, monocyte-macrophage lineage RAW264...
February 2016: Immunology Letters
Iolanda Lazaro, Ainhoa Oguiza, Carlota Recio, Beñat Mallavia, Julio Madrigal-Matute, Julia Blanco, Jesus Egido, Jose-Luis Martin-Ventura, Carmen Gomez-Guerrero
Heat shock proteins (HSPs) are induced by cellular stress and function as molecular chaperones that regulate protein folding. Diabetes impairs the function/expression of many HSPs, including HSP70 and HSP90, key regulators of pathological mechanisms involved in diabetes complications. Therefore, we investigated whether pharmacological HSP90 inhibition ameliorates diabetes-associated renal damage and atheroprogression in a mouse model of combined hyperglycemia and hyperlipidemia (streptozotocin-induced diabetic apolipoprotein E-deficient mouse)...
October 2015: Diabetes
Jing-Hong Zhou, Zhi-Yuan Pan, Yan-Fang Zhang, Wen-Yu Cui, Chao-Liang Long, Hai Wang
OBJECTIVE: To investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation. METHODS: Atherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining...
November 2014: Chinese Journal of Applied Physiology
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