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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/29748334/genetic-variant-in-human-par-protease-activated-receptor-4-enhances-thrombus-formation-resulting-in-resistance-to-antiplatelet-therapeutics
#1
Benjamin E Tourdot, Hannah Stoveken, Derek Trumbo, Jennifer Yeung, Yogendra Kanthi, Leonard C Edelstein, Paul F Bray, Gregory G Tall, Michael Holinstat
OBJECTIVE: Platelet activation after stimulation of PAR (protease-activated receptor) 4 is heightened in platelets from blacks compared with those from whites. The difference in PAR4 signaling by race is partially explained by a single-nucleotide variant in PAR4 encoding for either an alanine or threonine at amino acid 120 in the second transmembrane domain. The current study sought to determine whether the difference in PAR4 signaling by this PAR4 variant is because of biased Gq signaling and whether the difference in PAR4 activity results in resistance to traditional antiplatelet intervention...
May 10, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29748333/hepatic-overexpression-of-endothelial-lipase-lowers-hdl-high-density-lipoprotein-but-maintains-reverse-cholesterol-transport-in-mice-role-of-sr-bi-scavenger-receptor-class-b-type-i-abca1-atp-binding-cassette-transporter-a1-dependent-pathways
#2
Shunichi Takiguchi, Makoto Ayaori, Emi Yakushiji, Takafumi Nishida, Kazuhiro Nakaya, Makoto Sasaki, Maki Iizuka, Harumi Uto-Kondo, Yoshio Terao, Makiko Yogo, Tomohiro Komatsu, Masatsune Ogura, Katsunori Ikewaki
OBJECTIVE: Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. APPROACH AND RESULTS: Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels...
May 10, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29724820/temporal-and-spatial-post-transcriptional-regulation-of-zebrafish-tie1-mrna-by-long-noncoding-rna-during-brain-vascular-assembly
#3
Tamjid A Chowdhury, Chris Koceja, Shahram Eisa-Beygi, Benjamin P Kleinstiver, Suresh N Kumar, Chien-Wei Lin, Keguo Li, Shubhangi Prabhudesai, J Keith Joung, Ramani Ramchandran
OBJECTIVE: Tie1 (tyrosine kinase containing immunoglobulin and epidermal growth factor homology 1), an endothelial and hematopoietic cell-specific receptor tyrosine kinase, is an important regulator of angiogenesis and critical for maintaining vascular integrity. The post-transcriptional regulation of tie1 mRNA expression is not understood, but it might partly explain Tie1's differential expression pattern in endothelium. Following up on our previous work that identified natural antisense transcripts from the tie1 locus- tie1 antisense ( tie1AS ), which regulates tie1 mRNA levels in zebrafish-we attempted to identify the mechanism of this regulation...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29724819/establishing-the-transient-mass-balance-of-thrombosis-from-tissue-factor-to-thrombin-to-fibrin-under-venous-flow
#4
Shu Zhu, Jason Chen, Scott L Diamond
OBJECTIVE: We investigated the coregulation of thrombin and fibrin as blood flows over a procoagulant surface. APPROACH AND RESULTS: Using microfluidic perfusion of factor XIIa-inhibited human whole blood (200 s- 1 wall shear rate) over a 250-μ long patch of collagen/TF (tissue factor; ≈1 molecule per μm2 ) and immunoassays of the effluent for F1.2 (prothrombin fragment 1.2), TAT (thrombin-antithrombin complex), and D-dimer (post-end point plasmin digest), we sought to establish the transient mass balance for clotting under venous flow...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29724818/hypoxia-and-ischemia-promote-a-maladaptive-platelet-phenotype
#5
Scott J Cameron, Doran S Mix, Sara K Ture, Rachel A Schmidt, Amy Mohan, Daphne Pariser, Michael C Stoner, Punit Shah, Lijun Chen, Hui Zhang, David J Field, Kristina L Modjeski, Sandra Toth, Craig N Morrell
OBJECTIVE: Reduced blood flow and tissue oxygen tension conditions result from thrombotic and vascular diseases such as myocardial infarction, stroke, and peripheral vascular disease. It is largely assumed that while platelet activation is increased by an acute vascular event, chronic vascular inflammation, and ischemia, the platelet activation pathways and responses are not themselves changed by the disease process. We, therefore, sought to determine whether the platelet phenotype is altered by hypoxic and ischemic conditions...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29724817/myeloid-%C3%AE-catenin-deficiency-exacerbates-atherosclerosis-in-low-density-lipoprotein-receptor-deficient-mice
#6
Fang Wang, Zun Liu, Se-Hyung Park, Taesik Gwag, Weiwei Lu, Murong Ma, Yipeng Sui, Changcheng Zhou
OBJECTIVE: The Wnt/β-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/β-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage β-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of β-catenin expression on macrophage functions and atherosclerosis development...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29724816/modulation-of-lin28b-let-7-signaling-by-propranolol-contributes-to-infantile-hemangioma-involution
#7
Ezinne Francess Mong, Kemal Marc Akat, John Canfield, John Lockhart, Jeffrey VanWye, Andrew Matar, John C M Tsibris, June Wu, Thomas Tuschl, Hana Totary-Jain
OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign vascular neoplasms of infancy, characterized by a rapid growth phase followed by a spontaneous involution, or triggered by propranolol treatment by poorly understood mechanisms. LIN28/let-7 axis plays a central role in the regulation of stem cell self-renewal and tumorigenesis. However, the role of LIN28B/let-7 signaling in IH pathogenesis has not yet been elucidated. APPROACH AND RESULTS: LIN28B is highly expressed in proliferative IH and is less expressed in involuted and in propranolol-treated IH samples as measured by immunofluorescence staining and quantitative RT-PCR...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29699973/association-of-total-and-differential-leukocyte-counts-with-cardiovascular-disease-and-mortality-in-the-uk-biobank
#8
Claire Welsh, Paul Welsh, Patrick B Mark, Carlos A Celis-Morales, James Lewsey, Stuart R Gray, Donald M Lyall, Stamatina Iliodromiti, Jason M R Gill, Jill Pell, Pardeep S Jhund, Naveed Sattar
OBJECTIVE: Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD. APPROACH AND RESULTS: Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7...
April 26, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29674476/glycosaminoglycan-neutralization-in-coagulation-control
#9
REVIEW
Amélie I S Sobczak, Samantha J Pitt, Alan J Stewart
The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate, and heparin are important anticoagulants that inhibit clot formation through interactions with antithrombin and heparin cofactor II. Unfractionated heparin, low-molecular-weight heparin, and heparin-derived drugs are often the main treatments used clinically to handle coagulatory disorders. A wide range of proteins have been reported to bind and neutralize these GAGs to promote clot formation. Such neutralizing proteins are involved in a variety of other physiological processes, including inflammation, transport, and signaling...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29674475/effect-of-sfrp5-secreted-frizzled-related-protein-5-on-the-wnt5a-wingless-type-family-member-5a-induced-endothelial-dysfunction-and-its-relevance-with-arterial-stiffness-in-human-subjects
#10
Yun Kyung Cho, Yu Mi Kang, Seung Eun Lee, Yoo La Lee, So Mi Seol, Woo Je Lee, Joong-Yeol Park, Chang Hee Jung
OBJECTIVE: SFRP5 (secreted frizzled-related protein 5) is an endogenous inhibitor of WNT5A (wingless-type family member 5a), which has been implicated in atherosclerosis. However, contradictory results have been reported about the role of SFRP5 in atherosclerosis. We aimed to investigate whether SFRP5 could restore WNT5A-induced endothelial dysfunction in vitro and ex vivo. In addition, we sought to determine whether the serum concentration of SFRP5 is associated with atherosclerosis in humans...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29674474/genetic-deletion-of-il-interleukin-19-exacerbates-atherogenesis-in-il19-%C3%A3-ldlr-double-knockout-mice-by-dysregulation-of-mrna-stability-protein-hur-human-antigen-r
#11
Mitali Ray, Khatuna Gabunia, Christine N Vrakas, Allison B Herman, Farah Kako, Sheri E Kelemen, Laurel A Grisanti, Michael V Autieri
OBJECTIVE: To test the hypothesis that loss of IL (interleukin)-19 exacerbates atherosclerosis. APPROACH AND RESULTS: Il19 -/- mice were crossed into Ldlr -/- (low-density lipoprotein receptor knock out) mice. Double knockout (dKO) mice had increased plaque burden in aortic arch and root compared with Ldlr -/- controls after 14 weeks of high-fat diet (HFD). dKO mice injected with 10 ng/g per day rmIL-19 had significantly less plaque compared with controls. qRT-PCR and Western blot analysis revealed dKO mice had increased systemic and intraplaque polarization of T cells and macrophages to proinflammatory Th 1 and M1 phenotypes, and also significantly increased TNF (tumor necrosis factor)-α expression in spleen and aortic arch compared with Ldlr -/- controls...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29650694/lymphatic-vasculature-requires-er-estrogen-receptor-%C3%AE-signaling-to-protect-from-lymphedema
#12
Florent Morfoisse, Florence Tatin, Benoit Chapût, Nicole Therville, Charlotte Vaysse, Raphael Métivier, Julie Malloizel-Delaunay, Francoise Pujol, Anne-Claire Godet, Fabienne De Toni, Frederic Boudou, Katia Grenier, David Dubuc, Eric Lacazette, Anne-Catherine Prats, Julie Guillermet-Guibert, Francoise Lenfant, Barbara Garmy-Susini
OBJECTIVE: Estrogens exert beneficial effect on the blood vascular system. However, their role on the lymphatic system has been poorly investigated. We studied the protective effect of the 17β estradiol-the most potent endogenous estrogen-in lymphedema-a lymphatic dysfunction, which results in a massive fluid and fat accumulation in the limb. APPROACH AND RESULTS: Screening of DNA motifs able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional activation of lymphangiogenesis-related gene expression including VEGF (vascular endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs (hyaluronan synthases)...
April 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29650693/high-mobility-group-box-1-from-hypoxic-trophoblasts-promotes-endothelial-microparticle-production-and-thrombophilia-in-preeclampsia
#13
Yae Hu, Ruhong Yan, Ce Zhang, Zhichao Zhou, Meng Liu, Can Wang, Hong Zhang, Liang Dong, Tiantian Zhou, Yi Wu, Ningzheng Dong, Qingyu Wu
OBJECTIVE: Thrombophilia is a major complication in preeclampsia, a disease associated with placental hypoxia and trophoblast inflammation. Preeclampsia women are known to have increased circulating microparticles that are procoagulant, but the underlying mechanisms remain unclear. In this study, we sought to understand the mechanism connecting placental hypoxia, circulating microparticles, and thrombophilia. APPROACH AND RESULTS: We analyzed protein markers on plasma microparticles from preeclampsia women and found that the increased circulating microparticles were mostly from endothelial cells...
April 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29650692/microrna-mediated-therapy-modulating-blood-brain-barrier-disruption-improves-vascular-cognitive-impairment
#14
Kensuke Toyama, Joshua M Spin, Alicia C Deng, Ting-Ting Huang, Ke Wei, Markus U Wagenhäuser, Takuya Yoshino, Huy Nguyen, Joscha Mulorz, Soumajit Kundu, Uwe Raaz, Matti Adam, Isabel N Schellinger, Ann Jagger, Philip S Tsao
OBJECTIVE: There are currently no effective treatments for the prevention of dementia associated with vascular cognitive impairment. MicroRNAs regulate gene expression at the post-transcriptional level and play key roles in vascular disorders. TNFα (tumor necrosis factor-α) regulates blood-brain barrier breakdown through modification of cerebral tight junctions. Here, we sought key TNFα-responsive microRNAs that might influence blood-brain barrier breakdown via cerebral tight junction disruption in vascular cognitive impairment...
April 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29622563/noncanonical-matrix-metalloprotease-1-protease-activated-receptor-1-signaling-drives-progression-of-atherosclerosis
#15
Rajashree Rana, Tianfang Huang, Georgios Koukos, Elizabeth K Fletcher, Susan E Turner, Andrew Shearer, Paul A Gurbel, Jeffrey J Rade, Carey D Kimmelstiel, Kevin P Bliden, Lidija Covic, Athan Kuliopulos
OBJECTIVE: Protease-activated receptor-1 (PAR1) is classically activated by thrombin and is critical in controlling the balance of hemostasis and thrombosis. More recently, it has been shown that noncanonical activation of PAR1 by matrix metalloprotease-1 (MMP1) contributes to arterial thrombosis. However, the role of PAR1 in long-term development of atherosclerosis is unknown, regardless of the protease agonist. APPROACH AND RESULTS: We found that plasma MMP1 was significantly correlated ( R =0...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29622562/settlement-of-stenotic-site-and-enhancement-of-risk-factor-load-for-atherosclerosis-in-left-anterior-descending-coronary-artery-by-myocardial-bridge
#16
Yuri Akishima-Fukasawa, Yukio Ishikawa, Tetuo Mikami, Yoshikiyo Akasaka, Toshiharu Ishii
OBJECTIVE: The aim of this study was to investigate the influence of a myocardial bridge (MB) on atherosclerosis development in the left anterior descending artery of the normal heart and the importance of traditional risk factors (RFs). An additional objective was to determine the correlation between intimal thickening and luminal narrowing. APPROACH AND RESULTS: The left anterior descending artery from 150 autopsied hearts was treated with formalin perfusion fixation, and each left anterior descending artery was serially cross-sectioned...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29622561/o-linked-%C3%AE-n-acetylglucosamine-modification-of-a20-enhances-the-inhibition-of-nf-%C3%AE%C2%BAb-nuclear-factor-%C3%AE%C2%BAb-activation-and-elicits-vascular-protection-after-acute-endoluminal-arterial-injury
#17
Dan Yao, Lijuan Xu, Oufan Xu, Rujun Li, Mingxing Chen, Hui Shen, Huajiang Zhu, Fengyi Zhang, Deshang Yao, Yiu-Fai Chen, Suzanne Oparil, Zhengang Zhang, Kaizheng Gong
OBJECTIVE: Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear. In this study, we test the hypothesis that increased A20 O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29622560/role-of-adamts-a-disintegrin-and-metalloproteinase-with-thrombospondin-motifs-5-in-aortic-dilatation-and-extracellular-matrix-remodeling
#18
Marika Fava, Javier Barallobre-Barreiro, Ursula Mayr, Ruifang Lu, Athanasios Didangelos, Ferheen Baig, Marc Lynch, Norman Catibog, Abhishek Joshi, Temo Barwari, Xiaoke Yin, Marjan Jahangiri, Manuel Mayr
OBJECTIVE: Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. APPROACH AND RESULTS: A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat )...
April 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29599141/switch-in-laminin-%C3%AE-2-to-laminin-%C3%AE-1-isoforms-during-aging-controls-endothelial-cell-functions
#19
Julian U G Wagner, Emmanouil Chavakis, Eva-Maria Rogg, Marion Muhly-Reinholz, Simone F Glaser, Stefan Günther, David John, Francesca Bonini, Andreas M Zeiher, Liliana Schaefer, Melanie-Jane Hannocks, Reinier A Boon, Stefanie Dimmeler
OBJECTIVE: Endothelial cells play important roles in tissue homeostasis and vascularization, a function that is impaired by aging. Here, we aim to decipher the role of the microenvironment underlying the impairment of endothelial cell functions by aging. APPROACH AND RESULTS: RNA sequencing of isolated cardiac endothelial cells derived from young and 18-month-old mouse hearts revealed that aging affects the endothelial expression of genes encoding extracellular matrix proteins, specifically the laminin β1 ( Lamb1 ) and laminin β2 ( Lamb2 ) chains...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29599140/follicular-b-cells-promote-atherosclerosis-via-t-cell-mediated-differentiation-into-plasma-cells-and-secreting-pathogenic-immunoglobulin-g
#20
Christopher Tay, Yu-Han Liu, Peter Kanellakis, Axel Kallies, Yi Li, Anh Cao, Hamid Hosseini, Peter Tipping, Ban-Hock Toh, Alex Bobik, Tin Kyaw
OBJECTIVE: B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40, and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. APPROACH AND RESULTS: Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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