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About This Cover
Volume 27, Issue 3; March 1, 2007
Editorials
ATVB In Focus
Vascular Biology
Atherosclerosis and Lipoproteins
Thrombosis
Letters to the Editor
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Editorials
Osteopontin: A Bona Fide Mediator of Abdominal Aortic Aneurysm?
Mazen Shaheen and Neal L. Weintraub
Arterioscler Thromb Vasc Biol. 2007;27:439-441, doi:10.1161/01.ATV.0000258640.30287.7b
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Extracellular SOD Inactivation in High-Volume Hypertension: Role of Hydrogen Peroxide
Tohru Fukai
Arterioscler Thromb Vasc Biol. 2007;27:442-444, doi:10.1161/01.ATV.0000258920.36436.8e
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PLA
2
-V: A Real Player in Atherogenesis
Katariina Öörni and Petri T. Kovanen
Arterioscler Thromb Vasc Biol. 2007;27:445-447, doi:10.1161/01.ATV.0000258412.58289.ee
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RhoA-Dependent Vascular Smooth Muscle CellSpecific Transcription: Adding Diaphanous Formins to the Puzzle
Erik Larsson, Xianghua Zhou, and Levent M. Akyürek
Arterioscler Thromb Vasc Biol. 2007;27:448-449, doi:10.1161/01.ATV.0000257573.32695.e1
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The Modern Art of Atherosclerosis: A Picture of Colorful Plants, Cholesterol, and Inflammation
Andrey Frolov and David Y. Hui
Arterioscler Thromb Vasc Biol. 2007;27:450-452, doi:10.1161/01.ATV.0000257134.75071.cb
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ATVB In Focus
Regulation of Hemostasis and Thrombosis: Insights from Murine Models
Daniel T. Eitzman
Arterioscler Thromb Vasc Biol. 2007;27:453, doi:10.1161/01.ATV.0000257138.15250.48
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Heparin Cofactor II Modulates the Response to Vascular Injury
Douglas M. Tollefsen
Arterioscler Thromb Vasc Biol. 2007;27:454-460; published online before print December 28 2006, doi:10.1161/01.ATV.0000256471.22437.88
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Role of Oxidative Stress in the Pathogenesis of Abdominal Aortic Aneurysms
Michael L. McCormick, Dan Gavrila, and Neal L. Weintraub
Arterioscler Thromb Vasc Biol. 2007;27:461-469; published online before print January 11 2007, doi:10.1161/01.ATV.0000257552.94483.14
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Vascular Biology
Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension
Oliver Jung, Stefan L. Marklund, Ning Xia, Rudi Busse, and Ralf P. Brandes
Arterioscler Thromb Vasc Biol. 2007;27:470-477; published online before print December 14 2006, doi:10.1161/01.ATV.0000254823.15843.1f
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Effects of human extracellular superoxide dismutase (ecSOD) were determined in the 1-kidney-1-clip-model (1K1C). ecSOD lowered blood pressure and improved endothelial function in ecSOD+/+ and ecSOD-/- but not eNOS-/- mice. EcSOD expression increased in 1K1C but the protein was partially inactive from the reaction with peroxynitrite and hydrogen peroxide.
Diaphanous 1 and 2 Regulate Smooth Muscle Cell Differentiation by Activating the Myocardin-Related Transcription Factors
Dean P. Staus, Alicia L. Blaker, Joan M. Taylor, and Christopher P. Mack
Arterioscler Thromb Vasc Biol. 2007;27:478-486; published online before print December 14 2006, doi:10.1161/01.ATV.0000255559.77687.c1
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The RhoA effectors, mDia1 and mDia2, are strongly expressed in aortic SMCs and dramatically upregulate SMC-specific gene expression by stimulating the nuclear localization of the myocardin-related transcription factors. These results suggest that RhoA/mDia/MRTF signaling may serve to regulate SMC phenotype in response to extrinsic factors.
Functional Arterial and Venous Fate Is Determined by Graded VEGF Signaling and Notch Status During Embryonic Stem Cell Differentiation
Fredrik Lanner, Marcus Sohl, and Filip Farnebo
Arterioscler Thromb Vasc Biol. 2007;27:487-493; published online before print December 21 2006, doi:10.1161/01.ATV.0000255990.91805.6d
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In this study we developed an ES cell in vitro differentiation system to address early specification of the developing vasculature into functional arteries and veins. We found arterial specification to be VEGF and Notch dependent, while inhibition of Notch signaling or low VEGF levels were permissive for venous differentiation.
Vascular Endothelial Growth Factor Synergistically Enhances Induction of E-Selectin by Tumor Necrosis Factor-
Anita K. Stannard, Rohit Khurana, Ian M. Evans, Vassiliki Sofra, David I.R. Holmes, and Ian Zachary
Arterioscler Thromb Vasc Biol. 2007;27:494-502; published online before print December 14 2006, doi:10.1161/01.ATV.0000255309.38699.6c
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VEGF alone caused no significant induction of cell adhesion molecule expression in endothelial cells or during neointima formation in vivo. However, VEGF pretreatment enhanced E-selectin expression induced by TNF-{alpha}. These results indicate that VEGF "primes" endothelial cells to enhance selective responses to proinflammatory cytokines
Chimeric VEGF-E
NZ7
/PlGF Specifically Binding to VEGFR-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization
Yujuan Zheng, Makoto Watanabe, Takeshi Kuraishi, Shosaku Hattori, Chieko Kai, and Masabumi Shibuya
Arterioscler Thromb Vasc Biol. 2007;27:503-511; published online before print December 28 2006, doi:10.1161/01.ATV.0000256459.06671.3c
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We report here that chimeric VEGF-ENZ7/PlGF molecules of low antigenicity accelerate skin wound healing with enhanced angiogenesis, less macrophage infiltration and lymphangiogenesis in both wild-type and diabetic mouse model. These findings clearly indicate that chimeric VEGF-ENZ7/PlGF molecules are superior to VEGF-A, and might be the potential drugs in therapeutic angiogenesis.
Endothelial E-Selectin Potentiates Neovascularization via Endothelial Progenitor CellDependent and Independent Mechanisms
Yasunobu Nishiwaki, Masayuki Yoshida, Hideki Iwaguro, Haruchika Masuda, Noriko Nitta, Takayuki Asahara, and Mitsuaki Isobe
Arterioscler Thromb Vasc Biol. 2007;27:512-518; published online before print December 14 2006, doi:10.1161/01.ATV.0000254812.23238.2b
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Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.
Anthocyanin Prevents CD40-Activated Proinflammatory Signaling in Endothelial Cells by Regulating Cholesterol Distribution
Min Xia, Wenhua Ling, Huilian Zhu, Qing Wang, Jing Ma, Mengjun Hou, Zhihong Tang, Lan Li, and Qinyuan Ye
Arterioscler Thromb Vasc Biol. 2007;27:519-524; published online before print December 7 2006, doi:10.1161/01.ATV.0000254672.04573.2d
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Intracellular tumor necrosis factor receptor-associated factors (TRAFs) translocation to lipid rafts is a key element in CD40-induced signaling. The purpose of this study was to investigate the influence of anthocyanin on CD40-mediated proinflammatory events in human endothelial cells and the underlying possible molecular mechanism.
Increased Insulin-Stimulated Expression of Arterial Angiotensinogen and Angiotensin Type 1 Receptor in Patients With Type 2 Diabetes Mellitus and Atheroma
Wassim Hodroj, Liliana Legedz, Nabil Foudi, Catherine Cerutti, Marie-Claude Bourdillon, Patrick Feugier, Michel Beylot, Jacques Randon, and Giampiero Bricca
Arterioscler Thromb Vasc Biol. 2007;27:525-531; published online before print December 14 2006, doi:10.1161/01.ATV.0000254814.63768.3b
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The involvement of local angiotensin system in atherosclerosis of type 2 diabetes was investigated in carotid endarterectomy specimens and derived VSMCs. We have shown basal overexpression of angiotensinogen and angiotensin type-1 receptor in carotid wall as well as an exaggerated insulin-induced stimulation of this expression in VSMCs from these patients.
KLF2 Suppresses TGF-ß Signaling in Endothelium Through Induction of Smad7 and Inhibition of AP-1
Reinier A. Boon, Joost O. Fledderus, Oscar L. Volger, Eva J.A. van Wanrooij, Evangelia Pardali, Frank Weesie, Johan Kuiper, Hans Pannekoek, Peter ten Dijke, and Anton J.G. Horrevoets
Arterioscler Thromb Vasc Biol. 2007;27:532-539; published online before print December 28 2006, doi:10.1161/01.ATV.0000256466.65450.ce
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TGF-ß signaling in endothelium is generally considered proatherogenic. The shear stress-induced transcription factor KLF2 inhibits endothelial TGF-ß signaling by inducing the inhibitory Smad7 and suppressing the cofactor AP-1. This mechanism may contribute to the KLF2-mediated atheroprotection of shear stress.
Stem Cell Factor Attenuates Vascular Smooth Muscle Apoptosis and Increases Intimal Hyperplasia After Vascular Injury
Chao-Hung Wang, Subodh Verma, I-Chang Hsieh, Agnes Hung, Ting-Tzu Cheng, Shin-Yi Wang, Yu-Chih Liu, William L. Stanford, Richard D. Weisel, Ren-Ke Li, and Wen-Jin Cherng
Arterioscler Thromb Vasc Biol. 2007;27:540-547; published online before print January 4 2007, doi:10.1161/01.ATV.0000257148.01384.7d
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Apoptotic stimulation of VSMCs upregulated c-kit mRNA transcription and c-kit protein expression, which attracted SCF-positive cells, thus contributing to neointimal formation. The SCF attenuated the apoptosis of VSMCs through the Akt-Bcl-2 pathway. This study demonstrated that the SCF/c-kit system protects VSMCs against apoptosis and maintained intimal hyperplasia after vascular injury.
Controlled Release of Basic Fibroblast Growth Factor From Gelatin Hydrogel Sheet Improves Structural and Physiological Properties of Vein Graft in Rat
Tomonori Haraguchi, Kenji Okada, Yasuhiko Tabata, Yoshimasa Maniwa, Yoshitake Hayashi, and Yutaka Okita
Arterioscler Thromb Vasc Biol. 2007;27:548-555; published online before print December 14 2006, doi:10.1161/01.ATV.0000254811.11741.2b
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SR-BI/apoE double knockout (dKO) mice exhibit occlusive atherosclerotic coronary heart disease (CHD) characterized by myocardial infarctions, cardiac dysfunction, and premature death. Analysis of SR-BI/apoE/hepatic lipase (HL) triple knockout mice demonstrated that HL-deficiency reduces atherosclerosis, improves cardiac structure/function, and extends lifespan in this CHD model.
Pravastatin Enhances Beneficial Effects of Olmesartan on Vascular Injury of Salt-Sensitive Hypertensive Rats, via Pleiotropic Effects
Eiichiro Yamamoto, Takuro Yamashita, Tomoko Tanaka, Keiichiro Kataoka, Yoshiko Tokutomi, Zhong-Fang Lai, Yi-Fei Dong, Shinji Matsuba, Hisao Ogawa, and Shokei Kim-Mitsuyama
Arterioscler Thromb Vasc Biol. 2007;27:556-563; published online before print December 14 2006, doi:10.1161/01.ATV.0000254855.24394.f9
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Olmesartan, pravastatin, and their combination were compared on vascular effects in salt-sensitive hypertensive rats (SS rats). Olmesartan or pravastatin improved vascular injury of SS rats, via different pleiotropic effects. Pravastatin enhanced vascular effect of olmesartan, via Akt and eNOS. ARB combined with statin is useful for treatment of salt-sensitive hypertension.
In Vivo Actions of Angiopoietins on Quiescent and Remodeling Blood and Lymphatic Vessels in Mouse Airways and Skin
Kyung Eun Kim, Chung-Hyun Cho, Hak-Zoo Kim, Peter Baluk, Donald M. McDonald, and Gou Young Koh
Arterioscler Thromb Vasc Biol. 2007;27:564-570; published online before print December 28 2006, doi:10.1161/01.ATV.0000256458.82320.be
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Angiopoietins 1, 2, 3, and 4 elicited different amounts of blood and lymphatic vascular remodeling in normal and wound healing tissues. COMP-Ang1 and Ang2 given together produced an amount of vascular remodeling in normal vessels intermediate between the individual angiopoietins but had additive effects on vascular remodeling in skin wounds.
Genomics of Foam Cells and Nonfoamy Macrophages From Rabbits Identifies Arginase-I as a Differential Regulator of Nitric Oxide Production
Anita C. Thomas, Graciela B. Sala-Newby, Yasmin Ismail, Jason L. Johnson, Gerard Pasterkamp, and Andrew C. Newby
Arterioscler Thromb Vasc Biol. 2007;27:571-577; published online before print December 28 2006, doi:10.1161/01.ATV.0000256470.23842.94
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Suppression subtraction hybridization showed upregulation of 3 and downregulation of 11 genes in rabbit foam cells compared with nonfoamy macrophages. FCMs had more MMP-12 but less arginase-I activity, leading to more NO production, which probably influences atherosclerosis.
Atherosclerosis and Lipoproteins
Macrophage Phospholipid Transfer Protein Contributes Significantly to Total Plasma Phospholipid Transfer Activity and Its Deficiency Leads to Diminished Atherosclerotic Lesion Development
Riikka Vikstedt, Dan Ye, Jari Metso, Reeni B. Hildebrand, Theo J.C. Van Berkel, Christian Ehnholm, Matti Jauhiainen, and Miranda Van Eck
Arterioscler Thromb Vasc Biol. 2007;27:578-586; published online before print December 14 2006, doi:10.1161/01.ATV.0000254815.49414.be
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Systemic phospholipid transfer protein (PLTP) deficiency in mice is associated with a decreased susceptibility to atherosclerosis, whereas overexpression of human PLTP in mice increases atherosclerotic lesion development. PLTP is also expressed by macrophage-derived foam cells in human atherosclerotic lesions, but the exact role of macrophage PLTP in atherosclerosis is unknown. To clarify the role of macrophage PLTP in atherogenesis, PLTP was selectively disrupted in hematopoietic cells, including macrophages, by transplantation of bone marrow from PLTP knockout (PLTP-/-) mice into irradiated low-density lipoprotein receptor knockout mice. Macrophage PLTP is a significant contributor to plasma PLTP activity and deficiency of PLTP in macrophages leads to lowered atherosclerotic lesion development in low-density lipoprotein receptor knockout mice on Western-type diet.
Phagocytic NADPH Oxidase-Dependent Superoxide Production Stimulates Matrix Metalloproteinase-9: Implications for Human Atherosclerosis
Guillermo Zalba, Ana Fortuño, Josune Orbe, Gorka San José, María U. Moreno, Miriam Belzunce, José Antonio Rodríguez, Oscar Beloqui, José Antonio Páramo, and Javier Díez
Arterioscler Thromb Vasc Biol. 2007;27:587-593; published online before print December 28 2006, doi:10.1161/01.ATV.0000256467.25384.c6
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Enhanced {middle dot}O2- production increased MMP-9 activation in monocytes. NADPH oxidase and MMP-9 colocalized in atherosclerotic plaques. Enhanced NADPH oxidase-dependent {middle dot}O2- production associated with enhanced plasma MMP-9 levels in asymptomatic individuals. Interestingly, subjects in the upper quartile of {middle dot}O2- production associated with subclinical carotid atherosclerosis.
Total Body ABCG1 Expression Protects Against Early Atherosclerotic Lesion Development in Mice
Ruud Out, Menno Hoekstra, Illiana Meurs, Paula de Vos, Johan Kuiper, Miranda Van Eck, and Theo J.C. Van Berkel
Arterioscler Thromb Vasc Biol. 2007;27:594-599; published online before print January 4 2007, doi:10.1161/01.ATV.0000257136.24308.0c
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It has been shown that absence of macrophage ABCG1 may differentially influence atherosclerotic lesions dependent on the experimental setting and/or stage of atherosclerotic lesion development. In the current study we show that total body ABCG1 expression protects against early atherosclerotic lesion development.
Group V Secretory Phospholipase A
2
Promotes Atherosclerosis: Evidence From Genetically Altered Mice
Meredith A. Bostrom, Boris B. Boyanovsky, Craig T. Jordan, Marilyn P. Wadsworth, Douglas J. Taatjes, Frederick C. de Beer, and Nancy R. Webb
Arterioscler Thromb Vasc Biol. 2007;27:600-606; published online before print January 4 2007, doi:10.1161/01.ATV.0000257133.60884.44
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GV sPLA2 has been implicated in atherosclerosis in vitro. We demonstrate in mice that overexpression of GV sPLA2 in bone marrow cells results in increased atherosclerosis, whereas deficiency results in a reduction of atherosclerosis. We provide the first in vivo evidence that GV sPLA2 promotes atherosclerosis.
The Sphingosine-1-Phosphate Analogue FTY720 Reduces Atherosclerosis in Apolipoprotein EDeficient Mice
Petra Keul, Markus Tölle, Susann Lucke, Karin von Wnuck Lipinski, Gerd Heusch, Mirjam Schuchardt, Markus van der Giet, and Bodo Levkau
Arterioscler Thromb Vasc Biol. 2007;27:607-613; published online before print December 7 2006, doi:10.1161/01.ATV.0000254679.42583.88
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The S1P analogue FTY720 potently induces immunosuppression and activates eNOS. Therefore, we tested its effect on atherosclerosis in ApoE-/- mice. FTY720 dramatically reduced lesion volume, macrophage and collagen content and potently inhibited thrombin-induced release of MCP-1 via S1P3. Thus FTY720 may suppress the machinery regulating monocyte/macrophage emigration to atherosclerotic lesions.
Enhanced Expression of the Homeostatic Chemokines CCL19 and CCL21 in Clinical and Experimental Atherosclerosis: Possible Pathogenic Role in Plaque Destabilization
Jan K. Damås, Camilla Smith, Erik Øie, Børre Fevang, Bente Halvorsen, Torgun Wæhre, Agnes Boullier, Unni Breland, Arne Yndestad, Olga Ovchinnikova, Anna-Karin L. Robertson, Wiggo J. Sandberg, John Kjekshus, Kjetil Taskén, Stig S. Frøland, Lars Gullestad, Göran K. Hansson, Oswald Quehenberger, and Pål Aukrust
Arterioscler Thromb Vasc Biol. 2007;27:614-620; published online before print December 14 2006, doi:10.1161/01.ATV.0000255581.38523.7c
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We show increased plasma levels of the homeostatic chemokines in CCL19 and CCL21 in clinical and experimental atherosclerosis. By promoting inflammatory responses in T-cells and by inducing a matrix degrading, prothrombotic, and inflammatory phenotype in macrophages, we suggest that these chemokines could contribute to atherogenesis and plaque destabilization.
Granulocyte Macrophage Colony-Stimulating Factor Regulates Dendritic Cell Content of Atherosclerotic Lesions
Zory Shaposhnik, Xuping Wang, Michael Weinstein, Brian J. Bennett, and Aldons J. Lusis
Arterioscler Thromb Vasc Biol. 2007;27:621-627; published online before print December 7 2006, doi:10.1161/01.ATV.0000254673.55431.e6
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Recent evidence suggests that dendritic cells may play an important role in atherosclerosis. We hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF)-deficient mice would have decreased dendritic cells in lesions. Our data suggest that GM-CSF regulates dendritic cell formation in lesions and that this influences plaque growth and stability.
Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties
Endre Dyrøy, Therese H. Røst, Reidar J. Pettersen, Bente Halvorsen, Oddrun A. Gudbrandsen, Thor Ueland, Ziad Muna, Fredrik Müller, Jan E. Nordrehaug, Pål Aukrust, and Rolf K. Berge
Arterioscler Thromb Vasc Biol. 2007;27:628-634; published online before print December 21 2006, doi:10.1161/01.ATV.0000255950.70774.d5
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We explored the antioxidant, antiinflammatory, and hypolipidemic effects of TSA, a selenium-substituted fatty acid. Through mechanisms that seem to involve PPAR activation, TSA protects LDL from oxidation, has antiinflammatory effects in human leukocyte, and has lipid lowering properties in rat liver and plasma.
Effects of Peroxisome Proliferator-Activated Receptor Ligands, Bezafibrate and Fenofibrate, on Adiponectin Level
Aki Hiuge, Alexander Tenenbaum, Norikazu Maeda, Michal Benderly, Masahiro Kumada, Enrique Z. Fisman, David Tanne, Zipora Matas, Toshiyuki Hibuse, Koichi Fujita, Hitoshi Nishizawa, Yehuda Adler, Michael Motro, Shinji Kihara, Iichiro Shimomura, Solomon Behar, and Tohru Funahashi
Arterioscler Thromb Vasc Biol. 2007;27:635-641; published online before print December 28 2006, doi:10.1161/01.ATV.0000256469.06782.d5
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Subanalysis of BIP study showed that bezafibrate significantly increased serum adiponectin and higher baseline adiponectin levels were associated with reduced risk of new diabetes. A series of experiments by using PPAR{alpha}-deficient mice and cells indicated that fibrates enhance adiponectin partly through adipose PPAR{alpha}.
Aortic Valve Calcification: Determinants and Progression in the Population
David Messika-Zeitoun, Lawrence F. Bielak, Patricia A. Peyser, Patrick F. Sheedy, Stephen T. Turner, Vuyisile T. Nkomo, Jerome F. Breen, Joseph Maalouf, Christopher Scott, A. Jamil Tajik, and Maurice Enriquez-Sarano
Arterioscler Thromb Vasc Biol. 2007;27:642-648; published online before print December 21 2006, doi:10.1161/01.ATV.0000255952.47980.c2
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Aortic valve calcification (AVC) in 262 population-based participants >=60 years was frequent (27%) with aging, with diabetes, and with coronary calcification. After 3.8{+/-}0.9 years, AVC score and prevalence increased. New AVC acquisition occurs with high LDL-cholesterol and progressive atherosclerosis. Larger established AVC determines faster AVC progression independently of atherosclerotic risk factors.
The Prevalence and Quantification of Atherosclerosis in an Elderly Population Assessed by Whole-Body Magnetic Resonance Angiography
T. Hansen, J. Wikström, L.O. Johansson, L. Lind, and H. Ahlström
Arterioscler Thromb Vasc Biol. 2007;27:649-654; published online before print December 14 2006, doi:10.1161/01.ATV.0000255310.47940.3b
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Whole-body MRA, a minimally invasive, nonradiation technique, was used in a large cohort of elderly citizens and could be used in an epidemiological setting for quantifying atherosclerosis in different vascular territories, excluding the coronary arteries, in a single examination.
Association Between Osteopontin and Human Abdominal Aortic Aneurysm
Jonathan Golledge, Juanita Muller, Neil Shephard, Paula Clancy, Linda Smallwood, Corey Moran, Anthony E. Dear, Lyle J. Palmer, and Paul E. Norman
Arterioscler Thromb Vasc Biol. 2007;27:655-660; published online before print December 14 2006, doi:10.1161/01.ATV.0000255560.49503.4e
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In this study the association of osteopontin (OPN) with human AAA was investigated. Serum OPN concentrations were related to AAA presence and growth; however, 5 polymorphisms in the OPN gene were not associated with AAA. Serum OPN may be a useful biomarker for AAA.
Improving Prediction of Ischemic Cardiovascular Disease in the General Population Using Apolipoprotein B: The Copenhagen City Heart Study
Marianne Benn, Børge G. Nordestgaard, Gorm Boje Jensen, and Anne Tybjærg-Hansen
Arterioscler Thromb Vasc Biol. 2007;27:661-670; published online before print December 14 2006, doi:10.1161/01.ATV.0000255580.73689.8e
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Apolipoprotein B (apoB) levels predict fatal myocardial infarction in men. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. In the present study we show that apoB level is a predictor of an increased risk of: ischemic heart disease and myocardial infarction not only in men but also in women; ischemic cerebrovascular disease and ischemic stroke in women; and any ischemic cardiovascular event in both genders.
Increasing Peripheral Artery Intima Thickness From Childhood to Seniority
Walter Osika, Frida Dangardt, Julia Grönros, Ulf Lundstam, Anna Myredal, Mats Johansson, Reinhard Volkmann, Tomas Gustavsson, Li Ming Gan, and Peter Friberg
Arterioscler Thromb Vasc Biol. 2007;27:671-676; published online before print December 28 2006, doi:10.1161/01.ATV.0000256468.95403.6f
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Using very high-resolution UBM (55 MHz), IT in peripheral arteries of both healthy subjects and patients was examined. Age was related to both MT and IT. Correlations were found between carotid IMT and IT/IMT. This new technique may aid in detecting early vascular abnormalities.
A Novel Loss of Function Mutation of
PCSK9
Gene in White Subjects With Low-Plasma Low-Density Lipoprotein Cholesterol
Tommaso Fasano, Angelo B. Cefalù, Enza Di Leo, Davide Noto, Daniela Pollaccia, Letizia Bocchi, Vincenza Valenti, Renato Bonardi, Ornella Guardamagna, Maurizio Averna, and Patrizia Tarugi
Arterioscler Thromb Vasc Biol. 2007;27:677-681; published online before print December 14 2006, doi:10.1161/01.ATV.0000255311.26383.2f
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Nonsense mutations in PCSK9 gene resulting in truncated PCSK9 protein were reported to be associated with reduced plasma LDL-C in blacks. Here we report a novel mutation producing a short truncated PCSK9 (Ala68fsLeu82X) in a kindred with familial hypobetalipoproteinemia and in a group of hypocholesterolemic white subjects.
Thrombosis
A Mechanistic Model for Paradoxical Platelet Activation by Ligand-Mimetic
IIb
ß
3
(GPIIb/IIIa) Antagonists
Nicole Bassler, Christoph Loeffler, Pierre Mangin, Yuping Yuan, Meike Schwarz, Christoph E. Hagemeyer, Steffen U. Eisenhardt, Ingo Ahrens, Christoph Bode, Shaun P. Jackson, and Karlheinz Peter
Arterioscler Thromb Vasc Biol. 2007;27:E9-E15; published online before print December 14 2006, doi:10.1161/01.ATV.0000255307.65939.59
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Limitations with intravenous and failure of oral {alpha}IIbß3 antagonists question the current concept of ligand-mimetic {alpha}IIbß3 blockade. We provide a model explaining paradoxical platelet activation as consequence of {alpha}IIbß3 antagonist-induced conformational change of {alpha}IIbß3. Concomitant blockade of the ADP-receptor P2Y12, activation-specific and allosteric blockade are described/discussed as alternative {alpha}IIbß3-blocking strategies.
A Variant of Recombinant Factor VIIa With Enhanced Procoagulant and Antifibrinolytic Activities in an In Vitro Model of Hemophilia
Geoffrey A. Allen, Egon Persson, Robert A. Campbell, Mirella Ezban, Ulla Hedner, and Alisa S. Wolberg
Arterioscler Thromb Vasc Biol. 2007;27:683-689; published online before print January 4 2007, doi:10.1161/01.ATV.0000257204.82396.2b
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We compared the effects of recombinant factor VIIa (rFVIIa) and analog NN1731 on procoagulant activity in hemophilia. This analog did not activate platelets, but exhibited higher platelet factor Xa and thrombin generation, and shortened the clotting time and increased fibrin formation and stability more than rFVIIa.
Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG CoA) Reductase Blunts Factor VIIa/Tissue Factor and Prothrombinase Activities via Effects on Membrane Phosphatidylserine
Dennis J. Dietzen, Keith L. Page, Tina A. Tetzloff, Alan Bohrer, and John Turk
Arterioscler Thromb Vasc Biol. 2007;27:690-696; published online before print December 21 2006, doi:10.1161/01.ATV.0000255949.51053.ce
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Data Supplement
HMG-CoA reductase inhibitors may alter coagulation via effects on phospholipid metabolism. Atorvastatin treatment of EA.hy926 cells in combination with lipid restriction reduced cell cholesterol, phosphatidylserine, sphingomyelin, and ceramide but did not alter tissue factor expression. The resulting reduction in membrane exposure of phosphatidylserine blunted factor VIIa/tissue factor and prothrombinase activities.
Letters to the Editor
Letter to the Editor: Decreased Atherosclerosis in Mice Deficient in Tumor Necrosis Factor-
Receptor-II (p75)
Unni M. Chandrasekharan, Lori Mavrakis, Jonathan D. Smith, Paul E. DiCorleto, and Tracy L. Bonfield
Arterioscler Thromb Vasc Biol. 2007;27:E16-E17, doi:10.1161/01.ATV.0000255551.33365.22
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Letter to the Editor: Autoreactive CD4
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CD28
T Cells and Acute Coronary Syndromes
Behnam Zal, Christina Baboonian, and Juan Carlos Kaski
Arterioscler Thromb Vasc Biol. 2007;27:E18, doi:10.1161/01.ATV.0000254856.95617.38
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Letter to the Editor: Autoreactive CD4
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CD28
T Cells and Acute Coronary Syndromes
Anna-Karin L. Robertson and Göran K. Hansson
Arterioscler Thromb Vasc Biol. 2007;27:E19, doi:10.1161/01.ATV.0000254821.40192.35
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