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Gene expression in atherosclerotic plaque culture

Chinedu Anene, Anne M Graham, James Boyne, Wayne Roberts
Platelet microparticle (PMP)-induced angiogenesis plays a key role in tumour metastasis and has been proposed to contribute towards cardiovascular disease by enhancing atherosclerotic plaque vulnerability. However, the mechanisms underlying PMP induced angiogenesis are ill defined. Recent reports demonstrate that PMPs deliver micro-RNAs (miRNAs) to recipient cells, controlling gene expression. We therefore evaluated whether miRNA transfer was a key regulator of PMP-induced angiogenesis. Co-culturing PMPs with human umbilical vein endothelial cells (HUVEC) on extracellular matrix gel induced robust capillary like structure formation...
April 20, 2018: Biochimica et Biophysica Acta
Mary C Zuniga, Gayatri Raghuraman, Wei Zhou
BACKGROUND: Resistin, an adipokine with inflammatory properties, has been associated with plaque vulnerability. Vascular smooth muscle cells and macrophages are the major cellular components in advanced atherosclerotic plaques and interdependently affect plaque stability. The purpose of this study was to examine the effects of resistin on the interactions of vascular smooth muscle cells and macrophages using co-culture systems. METHODS: Human monocytes were differentiated into macrophages...
April 2018: Surgery
Leticia Gonzalez, Alexander S Qian, Usama Tahir, Pei Yu, Bernardo L Trigatti
We generated myeloid specific sphingosine-1-phosphate receptor 1 ( S1pr1 ) deficient mice by crossing mice that had myeloid specific expression of Cre recombinase ( lyzMCre ) with mice having the S1pr1 gene flanked by loxP recombination sites. We transplanted bone marrow from these mice and control lyzMCre mice with intact macrophage S1pr1 gene expression into low-density lipoprotein (LDL) receptor gene ( Ldlr ) deficient mice. The resulting chimeras were fed a high fat atherogenic diet for nine or twelve weeks and evaluated for atherosclerosis development in the aortic sinus...
December 15, 2017: International Journal of Molecular Sciences
Anusha N Seneviratne, Andreas Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq Khoyratty, David Saliba, Michael E Goddard, Stephen N Sansom, Isabel Goncalves, Rob Krams, Irina A Udalova, Claudia Monaco
BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models...
September 19, 2017: Circulation
Changpo Lin, Xiao Tang, Lirong Xu, Ruizhe Qian, Zhenyu Shi, Lixin Wang, Tingting Cai, Dong Yan, Weiguo Fu, Daqiao Guo
BACKGROUND: The clock genes are involved in regulating cardiovascular functions, and their expression disorders would lead to circadian rhythm disruptions of clock-controlled genes (CCGs), resulting in atherosclerotic plaque formation and rupture. Our previous study revealed the rhythmic expression of clock genes were attenuated in human plaque-derived vascular smooth muscle cells (PVSMCs), but failed to detect the downstream CCGs expressions and the underlying molecular mechanism. In this study, we examined the difference of CCGs rhythmic expression between human normal carotid VSMCs (NVSMCs) and PVSMCs...
July 10, 2017: Lipids in Health and Disease
Marwa M Mahmoud, Jovana Serbanovic-Canic, Shuang Feng, Celine Souilhol, Rouyu Xing, Sarah Hsiao, Akiko Mammoto, Jing Chen, Markus Ariaans, Sheila E Francis, Kim Van der Heiden, Victoria Ridger, Paul C Evans
Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress...
June 13, 2017: Scientific Reports
Alexandra C Finney, Steven D Funk, Jonette M Green, Arif Yurdagul, Mohammad Atif Rana, Rebecca Pistorius, Miriam Henry, Andrew Yurochko, Christopher B Pattillo, James G Traylor, Jin Chen, Matthew D Woolard, Christopher G Kevil, A Wayne Orr
BACKGROUND: Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis. METHODS: Here, we assessed the role of EphA2 in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe(-)(/-)) and by assessing EphA2 function in multiple vascular cell culture models...
August 8, 2017: Circulation
Valvanera Fernández-Laso, Cristina Sastre, Nerea Méndez-Barbero, Jesús Egido, Jose L Martín-Ventura, Carmen Gómez-Guerrero, Luis M Blanco-Colio
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK/Tnfsf12) is a cytokine implicated in different steps associated with vascular remodeling. However, the role of TWEAK under hyperglycemic conditions is currently unknown. Using two different approaches, genetic deletion of Tnfsf12 and treatment with a TWEAK blocking mAb, we have analyzed the effect of TWEAK inhibition on atherosclerotic plaque progression and stability in streptozotocin-induced diabetic ApoE deficient mice. Genetic inactivation of Tnfsf12 reduced atherosclerosis extension and severity in diabetic ApoE deficient mice...
April 27, 2017: Scientific Reports
Dan-Dan Zhang, Wen-Tian Wang, Jian Xiong, Xue-Min Xie, Shen-Shen Cui, Zhi-Guo Zhao, Mulin Jun Li, Zhu-Qin Zhang, De-Long Hao, Xiang Zhao, Yong-Jun Li, Junwen Wang, Hou-Zao Chen, Xiang Lv, De-Pei Liu
Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs)...
April 10, 2017: Scientific Reports
Violeta Georgeta Trusca, Elena Valeria Fuior, Ioana Madalina Fenyo, Dimitris Kardassis, Maya Simionescu, Anca Violeta Gafencu
Apolipoprotein E (apoE) has anti-atherosclerotic properties, being involved in the transport and clearance of cholesterol-rich lipoproteins as well as in cholesterol efflux from cells. We hypothesized that glucocorticoids may exert anti-inflammatory properties by increasing the level of macrophage-derived apoE. Our data showed that glucocorticoids increased apoE expression in macrophages in vitro as well as in vivo. Dexamethasone increased ~6 fold apoE mRNA levels in cultured peritoneal macrophages and RAW 264...
2017: PloS One
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 (P2Y2 R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2 R double knockout mice (ApoE-/- P2Y2 R-/- ) were used to determine the effect of P2Y2 R deficiency on vascular calcification in vivo...
February 2017: 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
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