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Arteriosclerosis, Thrombosis, and Vascular Biology

journal
https://www.readbyqxmd.com/read/27908894/contraction-of-blood-clots-is-impaired-in-acute-ischemic-stroke
#1
Valerie Tutwiler, Alina D Peshkova, Izabella A Andrianova, Dina R Khasanova, John W Weisel, Rustem I Litvinov
OBJECTIVE: Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. APPROACH AND RESULTS: We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908893/tracking-monocyte-recruitment-and-macrophage-accumulation-in-atherosclerotic-plaque-progression-using-a-novel-hcd68gfp-apoe-reporter-mouse
#2
Eileen McNeill, Asif J Iqbal, Daniel Jones, Jyoti Patel, Patricia Coutinho, Lewis Taylor, David R Greaves, Keith M Channon
OBJECTIVE: To create a model of atherosclerosis using green fluorescent protein (GFP)-targeted monocytes/macrophages, allowing analysis of both endogenous GFP(+) and adoptively transferred GFP(+) myeloid cells in arterial inflammation. APPROACH AND RESULTS: hCD68GFP reporter mice were crossed with ApoE(-/-) mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II-induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP(+) expression in CD11b(+)/CD64(+), CD11c(+)/MHC-II(HI), and CD11b(+)/F4/80(+) myeloid cells...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908892/resting-heart-rate-trajectory-pattern-predicts-arterial-stiffness-in-a-community-based-chinese-cohort
#3
Shuhua Chen, Weijuan Li, Cheng Jin, Anand Vaidya, Jingli Gao, Hui Yang, Shouling Wu, Xiang Gao
OBJECTIVE: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of having arterial stiffness in a large ongoing cohort study. APPROACH AND RESULTS: This community-based cohort included 12 554 participants in the Kailun study, who were free of myocardial infarction, stroke, arrhythmia, and cancer. We used latent mixture modeling to identify RHR trajectories in 2006, 2008, and 2010. We used multivariate linear regression model to examine the association between RHR trajectory patterns and the risk of having arterial stiffness, which was assessed by brachial-ankle pulse wave velocity in 2010 to 2016...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908891/the-paraoxonase-gene-cluster-protects-against-abdominal-aortic-aneurysm-formation
#4
Yun-Fei Yan, Jian-Fei Pei, Ran Zhang, Fang Wang, Peng Gao, Zhu-Qin Zhang, Ting-Ting Wang, Yang Zhang, Zhi-Gang She, Hou-Zao Chen, De-Pei Liu
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular pathology, the pathogenesis of which is closely related to oxidative stress. However, an effective pharmaceutical treatment is lacking because the exact cause of AAA remains unknown. Here, we aimed at delineating the role of the paraoxonases (PONs) gene cluster (PC), which prevents atherosclerosis through the detoxification of oxidized substrates, in AAA formation. APPROACH AND RESULTS: PC transgenic (Tg) mice were crossed to an Apoe(-/-) background, and an angiotensin II-induced AAA mouse model was used to analyze the effect of the PC on AAA formation...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908890/pathology-of-human-coronary-and-carotid-artery-atherosclerosis-and-vascular-calcification-in-diabetes-mellitus
#5
Kazuyuki Yahagi, Frank D Kolodgie, Christoph Lutter, Hiroyoshi Mori, Maria E Romero, Aloke V Finn, Renu Virmani
The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#6
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27879253/the-yin-yang-dynamics-of-dna-methylation-is-the-key-regulator-for-smooth-muscle-cell-phenotype-switch-and-vascular-remodeling
#7
Jianhui Zhuang, Peipei Luan, Hailing Li, Kai Wang, Pei Zhang, Yawei Xu, Wenhui Peng
OBJECTIVE: DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis. APPROACH AND RESULTS: In ApoE(-/-) mice fed a Western diet, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27879252/high-density-lipoprotein-associated-apolipoprotein-m-limits-endothelial-inflammation-by-delivering-sphingosine-1-phosphate-to-the-sphingosine-1-phosphate-receptor-1
#8
Mario Ruiz, Cecilia Frej, Andreas Holmér, Li J Guo, Sinh Tran, Björn Dahlbäck
OBJECTIVE: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27879251/altered-smooth-muscle-cell-force-generation-as-a-driver-of-thoracic-aortic-aneurysms-and-dissections
#9
REVIEW
Dianna M Milewicz, Kathleen M Trybus, Dongchuan Guo, H Lee Sweeney, Ellen Regalado, Kristine Kamm, James T Stull
The importance of maintaining contractile function in aortic smooth muscle cells (SMCs) is evident by the fact that heterozygous mutations in the major structural proteins or kinases controlling contraction lead to the formation of aneurysms of the ascending thoracic aorta that predispose to life-threatening aortic dissections. Force generation by SMC requires ATP-dependent cyclic interactions between filaments composed of SMC-specific isoforms of α-actin (encoded by ACTA2) and myosin heavy chain (MYH11). ACTA2 and MYH11 mutations shown to disrupt this cyclic interaction predispose to thoracic aortic disease...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856459/challenges-and-opportunities-in-linking-long-noncoding-rnas-to-cardiovascular-lung-and-blood-diseases
#10
REVIEW
Jane E Freedman, Joseph M Miano
The new millennium heralds an unanticipated surge of genomic information, most notably an expansive class of long noncoding RNAs (lncRNAs). These transcripts, which now outnumber all protein-coding genes, often exhibit the same characteristics as mRNAs (RNA polymerase II-dependent, 5' methyl-capped, multiexonic, polyadenylated); yet, they do not encode for stable, well-conserved proteins. Elucidating the function of all relevant lncRNAs in heart, vasculature, lung, and blood is essential for generating a complete interactome in these tissues...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856458/focal-adhesion-kinase-promotes-the-progression-of-aortic-aneurysm-by-modulating-macrophage-behavior
#11
Takasuke Harada, Koichi Yoshimura, Osamu Yamashita, Koshiro Ueda, Noriyasu Morikage, Yasuhiro Sawada, Kimikazu Hamano
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear. APPROACH AND RESULTS: We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856457/carriers-of-the-pcsk9-proprotein-convertase-subtilisin-kexin-9-r46l-variant-are-characterized-by-an-antiatherogenic-lipoprotein-profile-assessed-by-nuclear-magnetic-resonance-spectroscopy
#12
Rutger Verbeek, Marjorie Boyer, S Matthijs Boekholdt, G Kees Hovingh, John J P Kastelein, Nicholas Wareham, Kay-Tee Khaw, Benoit J Arsenault
OBJECTIVE: Carriers of the PCSK9 (proprotein convertase subtilisin/kexin 9) R46L genetic variant (rs11591147) are characterized by low levels of low-density lipoprotein cholesterol and a decreased risk of cardiovascular disease. We studied the impact of the R46L variant on lipoprotein size and composition. APPROACH AND RESULTS: Lipoprotein size and composition were measured by nuclear magnetic resonance spectroscopy in 2373 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856455/map3k8-modulates-monocyte-state-and-atherogenesis-in-apoe-mice
#13
Carlos Sanz-Garcia, Ángela Sánchez, Constanza Contreras-Jurado, Carmela Cales, Cristina Barranquero, Marta Muñóz, Ramón Merino, Paula Escudero, Maria-Jesús Sanz, Jesús Osada, Ana Aranda, Susana Alemany
OBJECTIVE: Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R, adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS: We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD)...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856454/endothelial-cell-specific-deletion-of-p2y2-receptor-promotes-plaque-stability-in-atherosclerosis-susceptible-apoe-null-mice
#14
Chen Xingjuan, Shaomin Qian, April Hoggatt, Hongying Tang, Timothy A Hacker, Alexander G Obukhov, Paul B Herring, Cheikh I Seye
OBJECTIVE: Nucleotide P2Y2 receptor (P2Y2R) contributes to vascular inflammation by increasing vascular cell adhesion molecule-1 expression in endothelial cells (EC), and global P2Y2R deficiency prevents fatty streak formation in apolipoprotein E null (ApoE(-/-)) mice. Because P2Y2R is ubiquitously expressed in vascular cells, we investigated the contribution of endothelial P2Y2R in the pathogenesis of atherosclerosis. APPROACH AND RESULTS: EC-specific P2Y2R-deficient mice were generated by breeding VEcadherin5-Cre mice with the P2Y2R floxed mice...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856453/rasgrf-couples-nox4-dependent-endoplasmic-reticulum-signaling-to-ras
#15
Ru Feng Wu, Chengxu Liao, Hadi Hatoum, Guosheng Fu, Christhiaan D Ochoa, Lance S Terada
OBJECTIVES: In response to endoplasmic reticulum (ER) stress, endothelial cells initiate corrective pathways such as the unfolded protein response. Recent studies suggest that reactive oxygen species produced on the ER may participate in homeostatic signaling through Ras in response to ER stress. We sought to identify mechanisms responsible for this focal signaling pathway. APPROACH AND RESULTS: In endothelial cells, we found that ER stress induced by tunicamycin activates the NADPH oxidase Nox4 focally on the ER surface but not on the plasma membrane...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27834692/factor-xii-as-a-therapeutic-target-in-thromboembolic-and-inflammatory-diseases
#16
REVIEW
Katrin F Nickel, Andy T Long, Tobias A Fuchs, Lynn M Butler, Thomas Renné
Coagulation factor XII (FXII, Hageman factor) is a plasma protease that in its active form (FXIIa) initiates the procoagulant and proinflammatory contact system. This name arises from FXII's unique mechanism of activation that is induced by binding (contact) to negatively charged surfaces. Various substances have the capacity to trigger FXII contact-activation in vivo including mast cell-derived heparin, misfolded protein aggregates, collagen, nucleic acids, and polyphosphate. FXII deficiency is not associated with bleeding, and for decades, the factor was considered to be dispensable for coagulation in vivo...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27834691/zebrafish-model-for-functional-screening-of-flow-responsive-genes
#17
Jovana Serbanovic-Canic, Amalia de Luca, Christina Warboys, Pedro F Ferreira, Le A Luong, Sarah Hsiao, Ismael Gauci, Marwa Mahmoud, Shuang Feng, Celine Souilhol, Neil Bowden, John-Paul Ashton, Henning Walczak, David Firmin, Rob Krams, Justin C Mason, Dorian O Haskard, Spencer Sherwin, Victoria Ridger, Timothy J A Chico, Paul C Evans
OBJECTIVE: Atherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27834690/rac2-modulates-atherosclerotic-calcification-by-regulating-macrophage-interleukin-1%C3%AE-production
#18
Nicolle Ceneri, Lina Zhao, Bryan D Young, Abigail Healy, Suleyman Coskun, Hema Vasavada, Timur O Yarovinsky, Kenneth Ike, Ruggero Pardi, Lingfen Qin, Li Qin, George Tellides, Karen Hirschi, Judith Meadows, Robert Soufer, Hyung J Chun, Mehran Sadeghi, Jeffrey R Bender, Alan R Morrison
OBJECTIVE: The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial. Inflammation is likely a key mediator of vascular calcification, but immune signaling mechanisms that promote this process are minimally understood. APPROACH AND RESULTS: Here, we identify Rac2 as a major inflammatory regulator of signaling that directs plaque osteogenesis...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27834689/nicotine-accelerates-atherosclerosis-in-apolipoprotein-e-deficient-mice-by-activating-%C3%AE-7-nicotinic-acetylcholine-receptor-on-mast-cells
#19
Chen Wang, Han Chen, Wei Zhu, Yinchuan Xu, Ming-Fei Liu, Lian-Lian Zhu, Fan Yang, Ling Zhang, Xian-Bao Liu, Zhiwei Zhong, Jing Zhao, Jun Jiang, Meixiang Xiang, Hong Yu, Xinyang Hu, Hong Lu, Jian'an Wang
OBJECTIVE: Cigarette smoking is an independent risk factor for atherosclerosis. Nicotine, the addictive component of cigarettes, induces mast cell (MC) release and contributes to atherogenesis. The purpose of this study was to determine whether nicotine accelerates atherosclerosis through MC-mediated mechanisms and whether MC stabilizer prevents this pathological process. APPROACH AND RESULTS: Nicotine administration increased the size of atherosclerotic lesions in apolipoprotein E-deficient (Apoe(-/-)) mice fed a fat-enriched diet...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27834687/endothelial-scube2-interacts-with-vegfr2-and-regulates-vegf-induced-angiogenesis
#20
Yuh-Charn Lin, Tsu-Yi Chao, Chi-Tai Yeh, Steve R Roffler, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis, exerts its proangiogenic action by binding to VEGFR2 (VEGF receptor 2), the activity of which is further modulated by VEGFR2 coreceptors such as neuropilins. However, whether VEGFR2 is regulated by additional coreceptors is not clear. To investigate whether SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), a peripheral membrane protein expressed in vascular endothelial cells (ECs) known to bind other signaling receptors, functions as a VEGFR2 coreceptor and to verify the role of SCUBE2 in the VEGF-induced angiogenesis...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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