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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#1
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082260/mechanisms-of-mas1-receptor-mediated-signaling-in-the-vascular-endothelium
#2
Brian R Hoffmann, Timothy J Stodola, Jordan R Wagner, Daniela N Didier, Eric C Exner, Julian H Lombard, Andrew S Greene
OBJECTIVE: Angiotensin II (AngII) has been shown to regulate angiogenesis and at high pathophysiological doses to cause vasoconstriction through the AngII receptor type 1. Angiotensin 1 to 7 (Ang-(1-7)) acting through the Mas1 receptor can act antagonistically to high pathophysiological levels of AngII by inducing vasodilation, whereas the effects of Ang-(1-7) signaling on angiogenesis are less defined. To complicate the matter, there is growing evidence that a subpressor dose of AngII produces phenotypes similar to Ang-(1-7)...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082259/identification-of-genetic-variants-linking-protein-c-and-lipoprotein-metabolism-the-aric-study-atherosclerosis-risk-in-communities
#3
James S Pankow, Weihong Tang, Nathan Pankratz, Weihua Guan, Lu-Chen Weng, Mary Cushman, Eric Boerwinkle, Aarossn R Folsom
OBJECTIVE: Previous studies have identified common genetic variants in 4 chromosomal regions that together account for 14% to 15% of the variance in circulating levels of protein C. To further characterize the genetic architecture of protein C, we obtained denser coverage at some loci, extended investigation of protein C to low-frequency and rare variants, and searched for new associations in genes known to influence protein C. APPROACH AND RESULTS: Genetic associations with protein C antigen level were evaluated in ≤10 778 European and 3190 black participants aged 45 to 64 years...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082258/eepd1-is-a-novel-lxr-target-gene-in-macrophages-which-regulates-abca1-abundance-and-cholesterol-efflux
#4
Jessica Kristine Nelson, Duco Steven Koenis, Saskia Scheij, Emma Clare Laura Cook, Martina Moeton, Ana Santos, Jean-Marc Lobaccaro, Silvere Baron, Noam Zelcer
OBJECTIVE: The sterol-responsive nuclear receptors, liver X receptors α (LXRα, NR1H3) and β (LXRβ, NR1H2), are key determinants of cellular cholesterol homeostasis. LXRs are activated under conditions of high cellular sterol load and induce expression of the cholesterol efflux transporters ABCA1 and ABCG1 to promote efflux of excess cellular cholesterol. However, the full set of genes that contribute to LXR-stimulated cholesterol efflux is unknown, and their identification is the objective of this study...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062501/p2y12-promotes-migration-of-vascular-smooth-muscle-cells-through-cofilin-dephosphorylation-during-atherogenesis
#5
Xuan Niu, Shu-Lan Pi, Suraj Baral, Yuan-Peng Xia, Quan-Wei He, Ya-Nan Li, Hui-Juan Jin, Man Li, Meng-Die Wang, Ling Mao, Bo Hu
OBJECTIVE: P2Y12 is a well-recognized receptor expressed on platelets and the target of thienopyridine-type antiplatelet drugs. However, recent evidence suggests that P2Y12 expressed in vessel wall plays a role in atherogenesis, but the mechanisms remain elusive. In this study, we examined the molecular mechanisms of how vessel wall P2Y12 mediates vascular smooth muscle cells (VSMCs) migration and promotes the progression of atherosclerosis. APPROACH AND RESULTS: Using a high-fat diet-fed ApoE knockout mice model, we found that the expression of P2Y12 in VSMCs increased in a time-dependent manner and had a linear relationship with the plaque area...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062500/translational-relevance-and-recent-advances-of-animal-models-of-abdominal-aortic-aneurysm
#6
Jean Senemaud, Giuseppina Caligiuri, Harry Etienne, Sandrine Delbosc, Jean-Baptiste Michel, Raphaël Coscas
Human abdominal aortic aneurysm (AAA) pathophysiology is not yet completely understood. In conductance arteries, the insoluble extracellular matrix, synthesized by vascular smooth muscle cells, assumes the function of withstanding the intraluminal arterial blood pressure. Progressive loss of this function through extracellular matrix proteolysis is a main feature of AAAs. As most patients are now treated via endovascular approaches, surgical AAA specimens have become rare. Animal models provide valuable complementary insights into AAA pathophysiology...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062495/therapeutic-targeting-of-rna-polymerase-i-with-the-small-molecule-cx-5461-for-prevention-of-arterial-injury-induced-neointimal-hyperplasia
#7
Qing Ye, Shu Pang, Wenjing Zhang, Xiaotong Guo, Jianli Wang, Yongtao Zhang, Yang Liu, Xiao Wu, Fan Jiang
OBJECTIVE: RNA polymerase I (Pol I)-dependent rRNA synthesis is a determinant factor in ribosome biogenesis and thus cell proliferation. The importance of dysregulated Pol I activity in cardiovascular disease, however, has not been recognized. Here, we tested the hypothesis that specific inhibition of Pol I might prevent arterial injury-induced neointimal hyperplasia. APPROACH AND RESULTS: CX-5461 is a novel selective Pol I inhibitor. Using this tool, we demonstrated that local inhibition of Pol I blocked balloon injury-induced neointima formation in rat carotid arteries in vivo...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062494/cellular-repressor-of-e1a-stimulated-genes-is-a-critical-determinant-of-vascular-remodeling-in-response-to-angiotensin-ii
#8
Li Yang, Liu Yanxia, Tian Xiaoxiang, Zhang Yan, Song Haixu, Liu Meili, Zhang Xiaolin, Liu Haiwei, Zhang Jian, Zhang Quanyu, Liu Dan, Peng Chengfei, Yan Chenghui, Han Yaling
OBJECTIVE: Cellular repressor of E1A-stimulated genes (CREG) is a lysosomal glycoprotein implicated in maintaining vascular homeostasis. Here, we have hypothesized that CREG is a critical target of intervention for the prevention of hypertensive vascular remodeling. APPROACH AND RESULTS: CREG gene expression was significantly decreased accompanied by an upregulated expression of angiotensin II (Ang II) in remodeled vascular tissues of high salt-induced Dahl salt-sensitive rats and Ang II-induced mice...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062493/olfactomedin-2-regulates-smooth-muscle-phenotypic-modulation-and-vascular-remodeling-through-mediating-runt-related-transcription-factor-2-binding-to-serum-response-factor
#9
Ning Shi, Chen-Xiao Li, Xiao-Bing Cui, Stanislav I Tomarev, Shi-You Chen
OBJECTIVE: The objective of this study is to investigate the role and underlying mechanism of Olfactomedin 2 (Olfm2) in smooth muscle cell (SMC) phenotypic modulation and vascular remodeling. APPROACH AND RESULTS: Platelet-derived growth factor-BB induces Olfm2 expression in primary SMCs while modulating SMC phenotype as shown by the downregulation of SMC marker proteins. Knockdown of Olfm2 blocks platelet-derived growth factor-BB-induced SMC phenotypic modulation, proliferation, and migration...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062492/poliovirus-receptor-related-2-a-cholesterol-responsive-gene-affecting-atherosclerosis-development-by-modulating-leukocyte-migration
#10
Aránzazu Rossignoli, Ming-Mei Shang, Hanna Gladh, Christine Moessinger, Hassan Foroughi Asl, Husain Ahammad Talukdar, Oscar Franzén, Steffen Mueller, Johan L M Björkegren, Erika Folestad, Josefin Skogsberg
OBJECTIVE: Recently, poliovirus receptor-related 2 (Pvrl2) emerged as a top gene in a global gene expression study aiming to detect plasma cholesterol-responsive genes causally related to atherosclerosis regression in hypercholesterolemic mice. PVRL2 is an adherens junction protein implied to play a role in transendothelial migration of leukocytes, a key feature in atherosclerosis development. In this study, we investigated the effect of Pvrl2 deficiency on atherosclerosis development and transendothelial migration of leukocytes activity...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062491/reverse-cholesterol-transport-is-increased-in-germ-free-mice
#11
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
OBJECTIVE: The intestinal microbiota is emerging as a clinically relevant modulator of atherosclerotic risk. Reverse cholesterol transport (RCT) is an atheroprotective metabolic pathway. How the microbiota impacts RCT has not been investigated. Therefore, the aim of this study was to characterize cholesterol metabolism and RCT in germ-free mice compared with conventional mice. APPROACH AND RESULTS: In chow-fed germ-free mice, plasma cholesterol was unchanged, whereas liver cholesterol content was higher (1...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062490/dna-methylation-and-high-density-lipoprotein-functionality-the-regicor-study
#12
Sergi Sayols-Baixeras, Alvaro Hernáez, Issac Subirana, Carla Lluis-Ganella, Daniel Muñoz, Montserrat Fitó, Jaume Marrugat, Roberto Elosua
OBJECTIVE: The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established. APPROACH AND RESULTS: We designed an epigenome-wide association study including 645 individuals from the REGICOR study. We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062489/lipoprotein-a-mass-levels-increase-significantly-according-to-apoe-genotype-an-analysis-of-431%C3%A2-239-patients
#13
Patrick M Moriarty, Stephen A Varvel, Philip L S M Gordts, Joseph P McConnell, Sotirios Tsimikas
OBJECTIVE: Lipoprotein(a) [Lp(a)] levels are genetically determined by hepatocyte apolipoprotein(a) synthesis, but catabolic pathways also influence circulating levels. APOE genotypes have different affinities for the low-density lipoprotein (LDL) receptor and LDL-related protein-1, with ε2 having the weakest binding to LDL receptor at <2% relative to ε3 and ε4. APPROACH AND RESULTS: APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, and ε4/ε4), Lp(a) mass, directly measured Lp(a)-cholesterol levels, and a variety of apoB-related lipoproteins were measured in 431 239 patients...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062505/cross-sectional-positive-association-of-serum-lipids-and-blood-pressure-with-serum-sodium-within-the-normal-reference-range-of-135-145-mmol-l
#14
Shouguo Gao, Xiangqin Cui, Xujing Wang, Maurice B Burg, Natalia I Dmitrieva
OBJECTIVE: Serum sodium concentration is maintained by osmoregulation within normal range of 135 to 145 mmol/L. Previous analysis of data from the ARIC study (Atherosclerosis Risk in Communities) showed association of serum sodium with the 10-year risk scores of coronary heart disease and stroke. Current study evaluated the association of within-normal-range serum sodium with cardiovascular risk factors. APPROACH AND RESULTS: Only participants who did not take cholesterol or blood pressure medications and had sodium within normal 135 to 145 mmol/L range were included (n=8615), and the cohort was stratified based on race, sex, and smoking status...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062504/prothrombotic-fibrin-clot-phenotype-is-associated-with-recurrent-pulmonary-embolism-after-discontinuation-of-anticoagulant-therapy
#15
Michal Zabczyk, Krzysztof Plens, Wioletta Wojtowicz, Anetta Undas
OBJECTIVE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism with a high recurrence rate after anticoagulation cessation. Recently, we have reported that prothrombotic clot phenotype in venous thromboembolism patients is associated with an increased risk of recurrent deep-vein thrombosis. APPROACH AND RESULTS: We tested whether abnormal clot properties are predictive of recurrent PE. We investigated 156 consecutive white patients aged 18 to 65 years after the first-ever provoked or unprovoked PE (n=89), with or without deep-vein thrombosis...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062503/protective-aptitude-of-annexin-a1-in-arterial-neointima-formation-in-atherosclerosis-prone-mice
#16
Renske J de Jong, Nicole Paulin, Patricia Lemnitzer, Joana R Viola, Carla Winter, Bartolo Ferraro, Jochen Grommes, Christian Weber, Chris Reutelingsperger, Maik Drechsler, Oliver Soehnlein
OBJECTIVE: Restenosis as a consequence of arterial injury is aggravated by inflammatory pathways. Here, we investigate the role of the proresolving protein annexin A1 (AnxA1) in healing after wire injury. APPROACH AND RESULTS: Apoe(-/-) and Apoe(-/-)Anxa1(-/-) mice were subjected to wire injury while fed a high-cholesterol diet. Subsequently, localization of AnxA1 and AnxA1 plasma levels were examined. AnxA1 was found to localize within endothelial cells and macrophages in the neointima...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062502/targeting-elastase-for-molecular-imaging-of-early-atherosclerotic-lesions
#17
Almut Glinzer, Xiaopeng Ma, Jaya Prakash, Melanie A Kimm, Fabian Lohöfer, Katja Kosanke, Jaroslav Pelisek, Moritz P Thon, Sandra Vorlova, Katrin G Heinze, Hans-Henning Eckstein, Michael W Gee, Vasilis Nitziachristos, Alma Zernecke, Moritz Wildgruber
OBJECTIVE: Neutrophils accumulate in early atherosclerotic lesions and promote lesion growth. In this study, we evaluated an elastase-specific near-infrared imaging agent for molecular imaging using hybrid fluorescence molecular tomography/x-ray computed tomography. APPROACH AND RESULTS: Murine neutrophils were isolated from bone marrow and incubated with the neutrophil-targeted near-infrared imaging agent Neutrophil Elastase 680 FAST for proof of principle experiments, verifying that the elastase-targeted fluorescent agent is specifically cleaved and activated by neutrophil content after lysis or cell stimulation...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062499/role-of-kca3-1-channels-in-macrophage-polarization-and-its-relevance-in-atherosclerotic-plaque-instability
#18
Rende Xu, Chenguang Li, Yizhe Wu, Li Shen, Jianying Ma, Juying Qian, Junbo Ge
OBJECTIVE: Emerging evidence indicates that proinflammatory macrophage polarization imbalance plays a key role in atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in macrophage polarization is unknown. This study investigates the potential role of KCa3.1 in transcriptional regulation in macrophage polarization and its relationship to plaque instability...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062498/novel-thrombotic-function-of-a-human-snp-in-stxbp5-revealed-by-crispr-cas9-gene-editing-in-mice
#19
Qiuyu Martin Zhu, Kyung Ae Ko, Sara Ture, Michael A Mastrangelo, Ming-Huei Chen, Andrew D Johnson, Christopher J O'Donnell, Craig N Morrell, Joseph M Miano, Charles J Lowenstein
OBJECTIVE: To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWASs (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062497/increased-proangiogenic-activity-of-mobilized-cd34-progenitor-cells-of-patients-with-acute-st-segment-elevation-myocardial-infarction-role-of-differential-micro-rna-378-expression
#20
Christian Templin, Julia Volkmann, Maximilian Y Emmert, Pavani Mocharla, Maja Müller, Nicolle Kraenkel, Jelena R Ghadri, Martin Meyer, Beata Styp-Rekowska, Sylvie Briand, Roland Klingenberg, Milosz Jaguszewski, Christian M Matter, Valentin Djonov, Francois Mach, Stephan Windecker, Simon P Hoerstrup, Thomas Thum, Thomas F Lüscher, Ulf Landmesser
OBJECTIVE: Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. Micro-RNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34(+) progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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