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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28935759/lymphangiogenesis-facilitates-initial-lymph-formation-and-enhances-the-dendritic-cell-mobilizing-chemokine-ccl21-without-affecting-migration
#1
Tine V Karlsen, Tore Reikvam, Anne Tofteberg, Elham Nikpey, Trude Skogstrand, Marek Wagner, Olav Tenstad, Helge Wiig
OBJECTIVE: Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis. APPROACH AND RESULTS: To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935758/scavenger-receptor-cd36-directs-nonclassical-monocyte-patrolling-along-the-endothelium-during-early-atherogenesis
#2
Paola M Marcovecchio, Graham D Thomas, Zbigniew Mikulski, Erik Ehinger, Karin A L Mueller, Amy Blatchley, Runpei Wu, Yury I Miller, Anh Tram Nguyen, Angela M Taylor, Coleen A McNamara, Klaus Ley, Catherine C Hedrick
OBJECTIVE: Nonclassical monocytes (NCM) function to maintain vascular homeostasis by crawling or patrolling along the vessel wall. This subset of monocytes responds to viruses, tumor cells, and other pathogens to aid in protection of the host. In this study, we wished to determine how early atherogenesis impacts NCM patrolling in the vasculature. APPROACH AND RESULTS: To study the role of NCM in early atherogenesis, we quantified the patrolling behaviors of NCM in ApoE(-/-) (apolipoprotein E) and C57BL/6J mice fed a Western diet...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935757/resveratrol-inhibits-growth-of-experimental-abdominal-aortic-aneurysm-associated-with-upregulation-of-angiotensin-converting-enzyme-2
#3
Corey S Moran, Erik Biros, Smriti M Krishna, Yutang Wang, Chris Tikellis, Joseph V Moxon, Mark E Cooper, Paul E Norman, Louise M Burrell, Merlin C Thomas, Jonathan Golledge
OBJECTIVE: Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. APPROACH AND RESULTS: Ace2 deletion in apolipoprotein-deficient mice (ApoE(-/)(-)Ace2(-/y) ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935756/perinatal-hypercholesterolemia-exacerbates-atherosclerosis-lesions-in-offspring-by-altering-metabolism-of-trimethylamine-n-oxide-and-bile-acids
#4
Charlotte Trenteseaux, Anh-Thu Gaston, Audrey Aguesse, Guillaume Poupeau, Pierre de Coppet, Ramaroson Andriantsitohaina, Jamila Laschet, Valérie Amarger, Michel Krempf, Estelle Nobecourt-Dupuy, Khadija Ouguerram
OBJECTIVE: Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. APPROACH AND RESULTS: Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935755/leptin-induces-sca-1-progenitor-cell-migration-enhancing-neointimal-lesions-in-vessel-injury-mouse-models
#5
Yao Xie, Claire M F Potter, Alexandra Le Bras, Witold N Nowak, Wenduo Gu, Shirin Issa Bhaloo, Zhongyi Zhang, Yanhua Hu, Li Zhang, Qingbo Xu
OBJECTIVE: Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1(+) vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1(+) progenitor cells migration and neointimal formation and to understand the underlying mechanisms. APPROACH AND RESULTS: Sca-1(+) progenitor cells from the vessel wall of Lepr(+/+) and Lepr(-/)(-) mice were cultured and purified...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28912366/lower-plasma-fetuin-a-levels-are-associated-with-a-higher-mortality-risk-in-patients-with-coronary-artery-disease
#6
Xuechen Chen, Yuan Zhang, Qian Chen, Qing Li, Yanping Li, Wenhua Ling
OBJECTIVE: The present study was designed to evaluate the association of circulating fetuin-A with cardiovascular disease (CVD) and all-cause mortality. APPROACH AND RESULTS: We measured plasma fetuin-A in 1620 patients using an enzyme-linked immunosorbent assay kit. The patients were members of the Guangdong coronary artery disease cohort and were recruited between October 2008 and December 2011. Cox regression models were used to estimate the association between plasma fetuin-A and the risk of mortality...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28912365/d-dimer-in-african-americans-whole-genome-sequence-analysis-and-relationship-to-cardiovascular-disease-risk-in-the-jackson-heart-study
#7
Laura M Raffield, Neil A Zakai, Qing Duan, Cecelia Laurie, Joshua D Smith, Marguerite R Irvin, Margaret F Doyle, Rakhi P Naik, Ci Song, Ani W Manichaikul, Yongmei Liu, Peter Durda, Jerome I Rotter, Nancy S Jenny, Stephen S Rich, James G Wilson, Andrew D Johnson, Adolfo Correa, Yun Li, Deborah A Nickerson, Kenneth Rice, Ethan M Lange, Mary Cushman, Leslie A Lange, Alex P Reiner
OBJECTIVE: Plasma levels of the fibrinogen degradation product D-dimer are higher among African Americans (AAs) compared with those of European ancestry and higher among women compared with men. Among AAs, little is known of the genetic architecture of D-dimer or the relationship of D-dimer to incident cardiovascular disease. APPROACH AND RESULTS: We measured baseline D-dimer in 4163 AAs aged 21 to 93 years from the prospective JHS (Jackson Heart Study) cohort and assessed association with incident cardiovascular disease events...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28912364/novel-pathological-role-of-hnrnpa1-heterogeneous-nuclear-ribonucleoprotein-a1-in-vascular-smooth-muscle-cell-function-and-neointima-hyperplasia
#8
Li Zhang, Qishan Chen, Weiwei An, Feng Yang, Eithne Margaret Maguire, Dan Chen, Cheng Zhang, Guanmei Wen, Mei Yang, Bin Dai, Le Anh Luong, Jianhua Zhu, Qingbo Xu, Qingzhong Xiao
OBJECTIVE: hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved. APPROACH AND RESULTS: hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28912363/tgf%C3%AE-transforming-growth-factor-%C3%AE-blockade-induces-a-human-like-disease-in-a-nondissecting-mouse-model-of-abdominal-aortic-aneurysm
#9
Fabien Lareyre, Marc Clément, Juliette Raffort, Stefanie Pohlod, Meghana Patel, Bruno Esposito, Leanne Master, Alison Finigan, Marie Vandestienne, Nikolaos Stergiopulos, Soraya Taleb, Bram Trachet, Ziad Mallat
OBJECTIVE: Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. APPROACH AND RESULTS: Here, we test this hypothesis in the elastase-induced AAA model in mice...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882875/class-iii-pi3k-positively-regulates-platelet-activation-and-thrombosis-via-pi-3-p-directed-function-of-nadph-oxidase
#10
Yangyang Liu, Mengjiao Hu, Dongjiao Luo, Ming Yue, Shuai Wang, Xiaoyan Chen, Yangfan Zhou, Yi Wang, Yanchun Cai, Xiaolan Hu, Yuehai Ke, Zhongzhou Yang, Hu Hu
OBJECTIVE: Class III phosphoinositide 3-kinase, also known as vacuolar protein sorting 34 (VPS34), is a highly conserved enzyme regulating important cellular functions such as NADPH oxidase (NOX) assembly, membrane trafficking, and autophagy. Although VPS34 is expressed in platelets, its involvement in platelet activation remains unclear. Herein, we investigated the role of VPS34 in platelet activation and thrombus formation using VPS34 knockout mice. APPROACH AND RESULTS: Platelet-specific VPS34-deficient mice were generated and characterized...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882874/haploid-mammalian-genetic-screen-identifies-ubxd8-as-a-key-determinant-of-hmgcr-degradation-and-cholesterol-biosynthesis
#11
Anke Loregger, Matthijs Raaben, Josephine Tan, Saskia Scheij, Martina Moeton, Marlene van den Berg, Hila Gelberg-Etel, Elmer Stickel, Joseph Roitelman, Thijn Brummelkamp, Noam Zelcer
OBJECTIVE: The cellular demand for cholesterol requires control of its biosynthesis by the mevalonate pathway. Regulation of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), a rate-limiting enzyme in this pathway and the target of statins, is a key control point herein. Accordingly, HMGCR is subject to negative and positive regulations. In particular, the ability of oxysterols and intermediates of the mevalonate pathway to stimulate its proteasomal degradation is an exquisite example of metabolically controlled feedback regulation...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882873/abca8-regulates-cholesterol-efflux-and-high-density-lipoprotein-cholesterol-levels
#12
Laia Trigueros-Motos, Julian C van Capelleveen, Federico Torta, David Castaño, Lin-Hua Zhang, Caryn Chai, Martin Kang, Lidiya G Dimova, Alinda W M Schimmel, Ian Tietjen, Chris Radomski, Liang Juin Tan, Thiam Chung Hwee, Pradeep Narayanaswamy, Daniel Wu, Fabian Dorninger, Gopala Krishna Yakala, Amina Barhdadi, Veronique Angeli, Marie-Pierre Dubé, Johannes Berger, Geesje M Dallinga-Thie, Uwe J F Tietge, Markus R Wenk, Michael R Hayden, G Kees Hovingh, Roshni R Singaraja
OBJECTIVE: High-density lipoproteins (HDL) are considered to protect against atherosclerosis in part by facilitating the removal of cholesterol from peripheral tissues. However, factors regulating lipid efflux are incompletely understood. We previously identified a variant in adenosine triphosphate-binding cassette transporter A8 (ABCA8) in an individual with low HDL cholesterol (HDLc). Here, we investigate the role of ABCA8 in cholesterol efflux and in regulating HDLc levels. APPROACH AND RESULTS: We sequenced ABCA8 in individuals with low and high HDLc and identified, exclusively in low HDLc probands, 3 predicted deleterious heterozygous ABCA8 mutations (p...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882872/mechanical-activation-of-hypoxia-inducible-factor-1%C3%AE-drives-endothelial-dysfunction-at-atheroprone-sites
#13
Shuang Feng, Neil Bowden, Maria Fragiadaki, Celine Souilhol, Sarah Hsiao, Marwa Mahmoud, Scott Allen, Daniela Pirri, Blanca Tardajos Ayllon, Shamima Akhtar, A A Roger Thompson, Hanjoong Jo, Christian Weber, Victoria Ridger, Andreas Schober, Paul C Evans
OBJECTIVE: Atherosclerosis develops near branches and bends of arteries that are exposed to low shear stress (mechanical drag). These sites are characterized by excessive endothelial cell (EC) proliferation and inflammation that promote lesion initiation. The transcription factor HIF1α (hypoxia-inducible factor 1α) is canonically activated by hypoxia and has a role in plaque neovascularization. We studied the influence of shear stress on HIF1α activation and the contribution of this noncanonical pathway to lesion initiation...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882871/independent-and-synergistic-associations-of-biomarkers-of-vitamin-d-status-with-risk-of-coronary-heart-disease
#14
Lu Qi, Wenjie Ma, Yoriko Heianza, Yan Zheng, Tiange Wang, Dianjianyi Sun, Eric B Rimm, Frank B Hu, Edward Giovannucci, Christine M Albert, Kathryn M Rexrode, JoAnn E Manson
OBJECTIVE: To comprehensively evaluate the independent associations and potential interactions of vitamin D-related biomarkers including total and bioavailable 25-hydroxyvitamin D (25OHD), VDBP (vitamin D binding protein), and parathyroid hormone (PTH) with risk of coronary heart disease (CHD). APPROACH AND RESULTS: We prospectively identified incident cases of nonfatal myocardial infarction and fatal CHD among women in the Nurses' Health Study during 20 years of follow-up (1990-2010)...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882870/crispr-cas9-mediated-gene-editing-in-human-ipsc-derived-macrophage-reveals-lysosomal-acid-lipase-function-in-human-macrophages
#15
Hanrui Zhang, Jianting Shi, Melanie A Hachet, Chenyi Xue, Robert C Bauer, Hongfeng Jiang, Wenjun Li, Junichiro Tohyama, John Millar, Jeffrey Billheimer, Michael C Phillips, Babak Razani, Daniel J Rader, Muredach P Reilly
OBJECTIVE: To gain mechanistic insights into the role of LIPA(lipase A), the gene encoding LAL (lysosomal acid lipase) protein, in human macrophages. APPROACH AND RESULTS: We used CRISPR (clustered regularly interspaced short palindromic repeats )/Cas9 (CRISPR-associated protein 9) technology to knock out LIPA in human induced pluripotent stem cells and then differentiate to macrophage (human-induced pluripotent stem cells-derived macrophage [IPSDM]) to explore the human macrophage LIPA loss-of-function phenotypes...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882869/extracellular-vesicles-secreted-by-atherogenic-macrophages-transfer-microrna-to-inhibit-cell-migration
#16
My-Anh Nguyen, Denuja Karunakaran, Michele Geoffrion, Henry S Cheng, Kristofferson Tandoc, Ljubica Perisic Matic, Ulf Hedin, Lars Maegdefessel, Jason E Fish, Katey J Rayner
OBJECTIVE: During inflammation, macrophages secrete vesicles carrying RNA, protein, and lipids as a form of extracellular communication. In the vessel wall, extracellular vesicles (EVs) have been shown to be transferred between vascular cells during atherosclerosis; however, the role of macrophage-derived EVs in atherogenesis is not known. Here, we hypothesize that atherogenic macrophages secrete microRNAs (miRNAs) in EVs to mediate cell-cell communication and promote proinflammatory and proatherogenic phenotypes in recipient cells...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882868/genetic-ablation-of-microrna-33-attenuates-inflammation-and-abdominal-aortic-aneurysm-formation-via-several-anti-inflammatory-pathways
#17
Tetsushi Nakao, Takahiro Horie, Osamu Baba, Masataka Nishiga, Tomohiro Nishino, Masayasu Izuhara, Yasuhide Kuwabara, Hitoo Nishi, Shunsuke Usami, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Naoya Sowa, Satoko Ohno, Hiroki Aoki, Koji Hasagawa, Kazuhisa Sakamoto, Kenji Minatoya, Takeshi Kimura, Koh Ono
OBJECTIVE: Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that microRNA-33 inhibition and genetic ablation of microRNA-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. APPROACH AND RESULTS: MicroRNA-33a-5p expression in central zone of human AAA was higher than marginal zone...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28860223/differentiation-and-application-of-induced-pluripotent-stem-cell-derived-vascular-smooth-muscle-cells
#18
REVIEW
Eithne Margaret Maguire, Qingzhong Xiao, Qingbo Xu
Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment...
August 31, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28860222/variability-in-total-cholesterol-is-associated-with-the-risk-of-end-stage-renal-disease-a-nationwide-population-based-study
#19
Mee Kyoung Kim, Kyungdo Han, Eun Sil Koh, Hun-Sung Kim, Hyuk-Sang Kwon, Yong-Moon Park, Kun-Ho Yoon, Seung-Hwan Lee
OBJECTIVE: Recent data suggest that visit-to-visit variability of cholesterol is associated with cardiovascular events. We evaluated the role of lipid variability as a determinant of end-stage renal disease (ESRD). APPROACH AND RESULTS: Using nationally representative data from the Korean National Health Insurance System, 8 493 277 subjects who were free of ESRD and who underwent ≥3 health examinations during 2005 to 2010 were followed to the end of 2015. Total cholesterol (TC) variability was measured using the coefficient of variation, SD, and the variability independent of the mean...
August 31, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28860221/large-scale-analysis-of-determinants-stability-and-heritability-of-high-density-lipoprotein-cholesterol-efflux-capacity
#20
Andrea L Koekemoer, Veryan Codd, Nicholas G D Masca, Christopher P Nelson, Muntaser D Musameh, Bernhard M Kaess, Christian Hengstenberg, Daniel J Rader, Nilesh J Samani
OBJECTIVE: Cholesterol efflux capacity (CEC) has emerged as a biomarker of coronary artery disease risk beyond plasma high-density lipoprotein (HDL) cholesterol (HDL-C) level. However, the determinants of CEC are incompletely characterized. We undertook a large-scale family-based population study to identify clinical, biochemical, and HDL particle parameter determinants of CEC, characterize reasons for the discordancy with HDL-C, quantify its heritability, and assess its stability over 10 to 12 years...
August 31, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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