Arteriosclerosis, Thrombosis, and Vascular Biology -- Table of Contents (27 [4])

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Volume 27, Issue 4; April 1, 2007

Editorials
Brief Reviews
Vascular Biology
Atherosclerosis and Lipoproteins
Thrombosis
Letters to the Editor
Corrections

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	Editorials
	Two Views on Plaque Rupture Göran K. Hansson and Donald D. Heistad Arterioscler Thromb Vasc Biol. 2007;27:697, doi:10.1161/01.ATV.0000261344.03489.0c. Full Text \| PDF
	Serum Amyloid P Component and Cardiovascular Disease: Is There a Sensible Link? Wolfgang Koenig Arterioscler Thromb Vasc Biol. 2007;27:698-700, doi:10.1161/01.ATV.0000259353.77404.e0. Full Text \| PDF
	Small Is Beautiful: A Miniature Stent Model Mark J. Post and Johannes Waltenberger Arterioscler Thromb Vasc Biol. 2007;27:701-702, doi:10.1161/01.ATV.0000260002.49668.c5. Full Text \| PDF
	All Oxidase Roads Lead to Angiotensin, Too Lilach O. Lerman and Amir Lerman Arterioscler Thromb Vasc Biol. 2007;27:703-704, doi:10.1161/01.ATV.0000260389.74074.47. Full Text \| PDF
	Brief Reviews
	Plaque Rupture in Humans and Mice Stephen M. Schwartz, Zorina S. Galis, Michael E. Rosenfeld, and Erling Falk Arterioscler Thromb Vasc Biol. 2007;27:705-713; published online before print March 1 2007, doi:10.1161/01.ATV.0000261709.34878.20. Abstract \| Full Text \| PDF \| Data Supplement Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We will argue that such terminology may mislead readers by implying knowledge that does not yet exist.
	Assessment of Unstable Atherosclerosis in Mice Christopher L. Jackson, Martin R. Bennett, Erik A.L. Biessen, Jason L. Johnson, and Rob Krams Arterioscler Thromb Vasc Biol. 2007;27:714-720; published online before print March 1 2007, doi:10.1161/01.ATV.0000261873.86623.e1. Abstract \| Full Text \| PDF There is an urgent need for representative animal models where prospective examination of the events leading up to plaque rupture and the rupture process itself can be performed. Recently, reports have begun to emerge that apolipoprotein E and low density lipoprotein receptor knockout mice may spontaneously develop unstable atherosclerosis, with plaques in certain parts of the arterial tree showing features suggestive of plaque rupture. Here we discuss the problems inherent in applying definitions of plaque rupture as seen in human arteries to mice; the anatomic locations in mice where unstable plaques do and do not occur; methods of inducing plaque instability in mice; and how to assess plaque stability in mice. These considerations lead us to a number of general recommendations.
	Emerging Anticoagulant Drugs Jeffrey I. Weitz Arterioscler Thromb Vasc Biol. 2007;27:721, doi:10.1161/01.ATV.0000260470.02821.fe. Full Text \| PDF
	Factor IXa Inhibitors as Novel Anticoagulants Emily L. Howard, Kristian C.D. Becker, Christopher P. Rusconi, and Richard C. Becker Arterioscler Thromb Vasc Biol. 2007;27:722-727; published online before print February 1 2007, doi:10.1161/01.ATV.0000259363.91070.f1. Abstract \| Full Text \| PDF This review summarizes factor IXa inhibitors, an emerging class of anticoagulants that includes active site-blocked inhibitors, monoclonal antibodies, oral inhibitors, and RNA aptamers.
	Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Cécile V. Denis and Denisa D. Wagner Arterioscler Thromb Vasc Biol. 2007;27:728-739; published online before print February 1 2007, doi:10.1161/01.ATV.0000259359.52265.62. Abstract \| Full Text \| PDF This review focuses on key findings about the molecular mechanisms supporting hemostasis and thrombosis, obtained with genetically engineered mouse models deficient in various platelet adhesion receptors and ligands. Combination of these models with sophisticated methods allowing direct visualization of platelet-vessel wall interactions after injury greatly contributed to recent advances in the field.
	Vascular Biology
	Cholesterol Enhances Thrombin-Induced Release of Fibroblast Growth Factor-2 in Human Vascular Smooth Muscle Cells Bernhard H. Rauch, Godehard A. Scholz, Dana Baumgärtel-Allekotte, Petra Censarek, Jens W. Fischer, Artur-Aron Weber, and Karsten Schrör Arterioscler Thromb Vasc Biol. 2007;27:e20-e25; published online before print January 25 2007, doi:10.1161/01.ATV.0000258793.51013.34. Abstract \| Full Text \| PDF This study demonstrates that the mitogenic response toward thrombin is enhanced in cholesterol-enriched human vascular SMCs. Cholesterol-enrichment induces FGF-2 expression and its increased release by thrombin. These data suggest an important pathophysiological role of thrombin-induced mitogenesis and FGF-2 release under conditions of elevated cholesterol levels.
	Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo Anna-Liisa Levonen, Matias Inkala, Tommi Heikura, Suvi Jauhiainen, Henna-Kaisa Jyrkkänen, Emilia Kansanen, Kirsi Määttä, Elina Romppanen, Päivi Turunen, Juha Rutanen, and Seppo Ylä-Herttuala Arterioscler Thromb Vasc Biol. 2007;27:741-747; published online before print January 25 2007, doi:10.1161/01.ATV.0000258868.80079.4d. Abstract \| Full Text \| PDF \| Data Supplement We studied the effect of gene transfer of Nrf2, a transcription factor regulating antioxidant genes on VSMC growth, oxidative stress, and inflammation. Nrf2 overexpression induced antioxidant genes and inhibited VSMC proliferation in vitro, and reduced oxidative stress in vivo determined by oxLDL and inflammation assessed by macrophage number.
	Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress Thomas Thum, Daniela Fraccarollo, Sabrina Thum, Maximilian Schultheiss, Andreas Daiber, Philip Wenzel, Thomas Munzel, Georg Ertl, and Johann Bauersachs Arterioscler Thromb Vasc Biol. 2007;27:748-754; published online before print January 25 2007, doi:10.1161/01.ATV.0000258787.18982.73. Abstract \| Full Text \| PDF Endothelial progenitor cells play a fundamental role in vascular repair and are regulated by nitric oxide. Organic nitrates increased circulating EPC levels but varied in their effects on EPC function. Nitrates that do not increase oxidative stress in EPCs improved cellular function and may confer long-term cardiovascular protection.
	Reactive Oxygen Species Activate the HIF-1 ${alpha}$ Promoter Via a Functional NF ${kappa}$ B Site Steve Bonello, Christian Zähringer, Rachida S. BelAiba, Talija Djordjevic, John Hess, Carine Michiels, Thomas Kietzmann, and Agnes Görlach Arterioscler Thromb Vasc Biol. 2007;27:755-761; published online before print February 1 2007, doi:10.1161/01.ATV.0000258979.92828.bc. Abstract \| Full Text \| PDF \| Data Supplement ROS generated by exogenous H2O2 or by a NOX4-containing NADPH oxidase stimulated by thrombin, transcriptionally induced HIF-1{alpha} via a novel NF{kappa}B binding site in the HIF-1{alpha} promoter. Thus, ROS directly link these 2 major transcription factors, implicating an important role of this novel pathway in disorders associated with oxidative stress.
	Role of the Multidrug Resistance Protein-1 in Hypertension and Vascular Dysfunction Caused by Angiotensin II Julian D. Widder, Tomasz J. Guzik, Cornelius F.H. Mueller, Roza E. Clempus, Harald H.H.W. Schmidt, Sergey I. Dikalov, Kathy K. Griendling, Dean P. Jones, and David G. Harrison Arterioscler Thromb Vasc Biol. 2007;27:762-768; published online before print February 1 2007, doi:10.1161/01.ATV.0000259298.11129.a2. Abstract \| Full Text \| PDF \| Data Supplement This study demonstrates that glutathione loss via the multidrug resistance protein 1 (MRP1) modulates many aspects of vascular function during chronic angiotensin II infusion, including vascular glutathione levels, NO production, and endothelium-dependent vasodilatation, superoxide production, and tetrahydrobiopterin levels. The hypertension caused by angiotensin II was significantly blunted in MRP1-/- mice, suggesting that MRP1 could be a target for treatment of vascular oxidative stress and hypertension.
	Membrane-Type Serine Protease-1/Matriptase Induces Interleukin-6 and -8 in Endothelial Cells by Activation of Protease-Activated Receptor-2: Potential Implications in Atherosclerosis Isabell Seitz, Sibylle Hess, Henk Schulz, Robert Eckl, Gabriele Busch, Hans Peter Montens, Richard Brandl, Stefan Seidl, Albert Schömig, and Ilka Ott Arterioscler Thromb Vasc Biol. 2007;27:769-775; published online before print January 25 2007, doi:10.1161/01.ATV.0000258862.61067.14. Abstract \| Full Text \| PDF \| Data Supplement In endothelial cells, soluble MT-SP1/matriptase induced IL-8 and IL-6 expression. MT-SP1/matriptase proteolytic activity, activation of p38 MAPK and PKC{alpha} were required for cytokine release, which was abolished by downregulation of PAR-2. In the interaction of monocytes and endothelial cells MT-SP1/matriptase and PAR-2, respectively, were crucial for IL-8 release.
	Downregulation of Bone Morphogenetic Protein 4 Expression in Coronary Arterial Endothelial Cells: Role of Shear Stress and the cAMP/Protein Kinase A Pathway Anna Csiszar, Nazar Labinskyy, Kira E. Smith, Aracelie Rivera, Erik N.T.P. Bakker, Hanjoong Jo, Jason Gardner, Zsuzsanna Orosz, and Zoltan Ungvari Arterioscler Thromb Vasc Biol. 2007;27:776-782; published online before print February 1 2007, doi:10.1161/01.ATV.0000259355.77388.13. Abstract \| Full Text \| PDF \| Data Supplement Here we provide evidence that laminar shear stress and the cAMP/PKA pathway are important negative regulators of BMP-4 expression in the vascular endothelium. Because BMP-4 elicits endothelial activation and dysfunction, hypertension, and vascular calcification, inhibition of BMP-4 expression is likely to exert antiatherogenic and vasculoprotective effects.
	Cysteine-674 of the Sarco/Endoplasmic Reticulum Calcium ATPase Is Required for the Inhibition of Cell Migration by Nitric Oxide Jia Ying, XiaoYong Tong, David R. Pimentel, Robert M. Weisbrod, Mario P. Trucillo, Takeshi Adachi, and Richard A. Cohen Arterioscler Thromb Vasc Biol. 2007;27:783-790; published online before print January 18 2007, doi:10.1161/01.ATV.0000258413.72747.23. Abstract \| Full Text \| PDF \| Data Supplement Inhibition of migration of cultured HEK or rat aortic smooth muscle cells by nitric oxide is associated with S-glutathiolation and activation of the sarcoplasmic reticulum Ca2+ ATPase (SERCA). The S-glutathiolation and activation of SERCA, as well as the inhibition of migration, was prevented by overexpressing a C674S SERCA mutant.
	Exercise Training Restores Coronary Arteriolar Dilation to NOS Activation Distal to Coronary Artery Occlusion: Role of Hydrogen Peroxide Naris Thengchaisri, Robert Shipley, Yi Ren, Janet Parker, and Lih Kuo Arterioscler Thromb Vasc Biol. 2007;27:791-798; published online before print January 18 2007, doi:10.1161/01.ATV.0000258416.47953.9a. Abstract \| Full Text \| PDF \| Data Supplement This study demonstrates that endothelium-dependent NO-mediated dilation is impaired in SED LCX arterioles and that EX training restores the impaired function. It appears that H2O2, in addition to NO, contributes significantly to EX-induced restoration of endothelium-dependent dilation of coronary arterioles distal to occlusion.
	Mineralocorticoid Receptor Activation Promotes Vascular Cell Calcification Iris Z. Jaffe, Yin Tintut, Brenna G. Newfell, Linda L. Demer, and Michael E. Mendelsohn Arterioscler Thromb Vasc Biol. 2007;27:799-805; published online before print January 18 2007, doi:10.1161/01.ATV.0000258414.59393.89. Abstract \| Full Text \| PDF This study explores the role of aldosterone and its receptor the mineralocorticoid receptor (MR) in the process of VSMC calcification. In calcifying VSMCs, aldosterone stimulates alkaline phosphatase activity and mineralization. The mechanism requires VSMC MR activation and is independent of BMP2 signaling.
	Critical Role for Casein Kinase 2 and Phosphoinositide-3-Kinase in the Interferon- ${gamma}$ –Induced Expression of Monocyte Chemoattractant Protein-1 and Other Key Genes Implicated in Atherosclerosis Elizabeth J. Harvey, Na Li, and Dipak P. Ramji Arterioscler Thromb Vasc Biol. 2007;27:806-812; published online before print January 25 2007, doi:10.1161/01.ATV.0000258867.79411.96. Abstract \| Full Text \| PDF \| Data Supplement The mechanisms underlying the IFN-{gamma}-regulated expression of monocyte chemoattractant protein-1 and other key genes implicated in atherosclerosis were investigated. We show critical roles for CK2 and PI3K in addition to the JAK/STAT pathway in IFN-{gamma}-signaling in macrophages, which have implications in the development of atherosclerosis.
	Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis Makoto Sumi, Masataka Sata, Shin-ichiro Miura, Kerry-Anne Rye, Naoki Toya, Yuji Kanaoka, Katsuhiko Yanaga, Takao Ohki, Keijiro Saku, and Ryozo Nagai Arterioscler Thromb Vasc Biol. 2007;27:813-818; published online before print February 1 2007, doi:10.1161/01.ATV.0000259299.38843.64. Abstract \| Full Text \| PDF Reconstituted HDL (rHDL) augmented angiogenesis in ischemic hindlimb with enhanced incorporation of bone marrow-derived cells in new vessels. rHDL promoted differentiation of endothelial progenitor cells via PI3K/Akt pathway. The beneficial effect of rHDL was abrogated in eNOS-deficient mice. rHDL might be useful in therapeutic angiogenesis.
	VEGFR-1 and -2 Regulate Inflammation, Myocardial Angiogenesis, and Arteriosclerosis in Chronically Rejecting Cardiac Allografts Olivier Raisky, Antti I. Nykänen, Rainer Krebs, Maria Hollmén, Mikko A.I. Keränen, Jussi M. Tikkanen, Roope Sihvola, Leena Alhonen, Petri Salven, Yan Wu, Daniel J. Hicklin, Kari Alitalo, Petri K. Koskinen, and Karl B. Lemström Arterioscler Thromb Vasc Biol. 2007;27:819-825; published online before print February 8 2007, doi:10.1161/01.ATV.0000260001.55955.6c. Abstract \| Full Text \| PDF \| Data Supplement Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts. Our results suggest interplay of inflammation, primitive donor-derived myocardial angiogenesis, and arteriosclerosis in transplanted hearts, and that targeting VEGFR-1 and -2 differentially regulate these pathological reparative processes.
	Carbamylated Low-Density Lipoprotein Induces Monocyte Adhesion to Endothelial Cells Through Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Eugene O. Apostolov, Sudhir V. Shah, Ercan Ok, and Alexei G. Basnakian Arterioscler Thromb Vasc Biol. 2007;27:826-832; published online before print January 25 2007, doi:10.1161/01.ATV.0000258795.75121.8a. Abstract \| Full Text \| PDF \| Data Supplement The exposure of human coronary artery endothelial cells with carbamylated LDL but not native LDL caused U937 monocyte adhesion and the induction of ICAM-1 and VCAM-1 adhesion molecules. Silencing of ICAM-1 and VCAM-1 by siRNA or their inhibition using neutralizing antibody resulted in decreased monocyte adhesion to the endothelial cells.
	Increased In-Stent Stenosis in ApoE Knockout Mice: Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting Ziad A. Ali, Nicholas J. Alp, Henry Lupton, Nadine Arnold, Thomas Bannister, Yanhua Hu, Shafi Mussa, Mark Wheatcroft, David R. Greaves, Julian Gunn, and Keith M. Channon Arterioscler Thromb Vasc Biol. 2007;27:833-840; published online before print January 4 2007, doi:10.1161/01.ATV.0000257135.39571.5b. Abstract \| Full Text \| PDF \| Data Supplement In this study we describe the first mouse model of balloon angioplasty and stenting. This new model reproduces features of human percutaneous coronary intervention and provides the potential to investigate molecular pathways and evaluate novel therapeutic targets for stent injury and restenosis.
	Atherosclerosis and Lipoproteins
	Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE^–/– Mice Harry R. Davis, Jr, Lizbeth M. Hoos, Glen Tetzloff, Maureen Maguire, Li-ji Zhu, Michael P. Graziano, and Scott W. Altmann Arterioscler Thromb Vasc Biol. 2007;27:841-849; published online before print January 11 2007, doi:10.1161/01.ATV.0000257627.40486.46. Abstract \| Full Text \| PDF \| Data Supplement Niemann-Pick C1 Like 1 (Npc1l1)/apoE null-/- mice had a 77% reduction in cholesterol absorption. Fed chow or Western diets, plasma cholesterol was reduced, and atherosclerosis inhibited by >90% relative to apoE-/- mice. Lack of Npc1l1, the target of ezetimibe, in apoE-/- mice causes a nearly complete protection from atherogenesis.
	Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Michael Torzewski, Viola Ochsenhirt, Andrei L. Kleschyov, Matthias Oelze, Andreas Daiber, Huige Li, Heidi Rossmann, Sotirios Tsimikas, Kurt Reifenberg, Fei Cheng, Hans-Anton Lehr, Stefan Blankenberg, Ulrich Förstermann, Thomas Münzel, and Karl J. Lackner Arterioscler Thromb Vasc Biol. 2007;27:850-857; published online before print January 25 2007, doi:10.1161/01.ATV.0000258809.47285.07. Abstract \| Full Text \| PDF \| Data Supplement The present study analyzed the effect of glutathione peroxidase-1 (GPx-1) deficiency on atherogenesis in the apolipoprotein E-deficient mouse (ApoE-/-) on the C57BL/6J background. Our data demonstrate that deficiency of an antioxidative enzyme accelerates and modifies atherosclerotic lesion progression in ApoE-/- mice.
	Cholesteryl Ester Transfer Protein (CETP) Expression Protects Against Diet Induced Atherosclerosis in SR-BI Deficient Mice Christopher Harder, Paulina Lau, Andrew Meng, Stewart C. Whitman, and Ruth McPherson Arterioscler Thromb Vasc Biol. 2007;27:858-864; published online before print February 1 2007, doi:10.1161/01.ATV.0000259357.42089.dc. Abstract \| Full Text \| PDF To determine whether expression of the human CETP transgene protects against diet-induced atherosclerosis in SR-BI deficient (-/-) mice, we crossed these with CETP transgenic mice to create SR-BI-/- x CETPtg mice in a C57Bl/6 background. CETP expression reduced HDL cholesterol, increased HDL density, and markedly attenuated the development of atherosclerosis.
	Oral Administration of Tetrahydrobiopterin Slows the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice Yoshiyuki Hattori, Sachiko Hattori, Xi Wang, Hiroko Satoh, Nobuo Nakanishi, and Kikuo Kasai Arterioscler Thromb Vasc Biol. 2007;27:865-870; published online before print February 1 2007, doi:10.1161/01.ATV.0000258946.55438.0e. Abstract \| Full Text \| PDF \| Data Supplement Although it has been reported that oral administration of tetrahydrobiopterin (BH4) prevents endothelial dysfunction and vascular oxidative stress in various rat models, the effect of treatment with BH4 on atherogenesis remains unclear. Strategies such as oral administration of BH4 to ensure continuous BH4 availability may be effective in restoring nitric oxide-mediated endothelial function and limiting vascular disease and the progression of atherosclerosis.
	Anti–LOX-1 Rescues Endothelial Function in Coronary Arterioles in Atherosclerotic ApoE Knockout Mice Xiangbin Xu, Xue Gao, Barry J. Potter, Ji-Min Cao, and Cuihua Zhang Arterioscler Thromb Vasc Biol. 2007;27:871-877; published online before print February 1 2007, doi:10.1161/01.ATV.0000259358.31234.37. Abstract \| Full Text \| PDF We examined the role of LOX-1 in endothelial dysfunction in ApoE KO mice. Impaired vasodilation to ACh in ApoE KO mice is partially restored by NAD(P)H oxidase inhibitor. Anti-LOX-1 restored vasodilation to ACh; reduced mRNA expression of NAD(P)H oxidase and O2y- production. LOX-1 is implicated in endothelial dysfunction.
	A Diet-Induced Hypercholesterolemic Murine Model to Study Atherogenesis Without Obesity and Metabolic Syndrome Karsten Hartvigsen, Christoph J. Binder, Lotte F. Hansen, Apaïs Rafia, Joseph Juliano, Sohvi Hörkkö, Daniel Steinberg, Wulf Palinski, Joseph L. Witztum, and Andrew C. Li Arterioscler Thromb Vasc Biol. 2007;27:878-885; published online before print January 25 2007, doi:10.1161/01.ATV.0000258790.35810.02. Abstract \| Full Text \| PDF \| Data Supplement High-fat/high-cholesterol diets commonly used to induce atherogenesis in LDLR-/- mice also induce the metabolic syndrome. This study demonstrates that cholesterol enrichment of regular chow provides a simple atherogenic diet that moderately elevates LDL cholesterol generating a human-like lipoprotein profile and avoids confounding effects of the metabolic syndrome.
	CD44 Regulates Vascular Gene Expression in a Proatherogenic Environment Liang Zhao, Jason A. Hall, Natasha Levenkova, Eric Lee, Melissa K. Middleton, Alicia M. Zukas, Daniel J. Rader, John J. Rux, and Ellen Puré Arterioscler Thromb Vasc Biol. 2007;27:886-892; published online before print February 1 2007, doi:10.1161/01.ATV.0000259362.10882.c5. Abstract \| Full Text \| PDF \| Data Supplement We demonstrate that CD44 is selectively upregulated and functionally activated in lesion-prone aortic arch of apoE-/- mice before lesion development. Furthermore, gene expression profiling revealed a selective impact of CD44 on vascular gene expression in response to a proatherogenic environment illustrating that CD44 is an early mediator of atherogenesis.
	Role of Naturally Occurring CD4⁺CD25⁺ Regulatory T Cells in Experimental Atherosclerosis Adi Mor, David Planer, Galia Luboshits, Arnon Afek, Shula Metzger, Tova Chajek-Shaul, Gad Keren, and Jacob George Arterioscler Thromb Vasc Biol. 2007;27:893-900; published online before print February 1 2007, doi:10.1161/01.ATV.0000259365.31469.89. Abstract \| Full Text \| PDF \| Data Supplement Naturally occurring CD4+CD25+ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis. CD4+CD25+ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.
	IAP Survivin Regulates Atherosclerotic Macrophage Survival Olivier P. Blanc-Brude, Elisabeth Teissier, Yves Castier, Guy Lesèche, Ann-Pascal Bijnens, Mat Daemen, Bart Staels, Ziad Mallat, and Alain Tedgui Arterioscler Thromb Vasc Biol. 2007;27:901-907; published online before print January 25 2007, doi:10.1161/01.ATV.0000258794.57872.3f. Abstract \| Full Text \| PDF Macrophages express inhibitor of apoptosis (IAP) survivin in human aorta lipid streaks, or after growth factors stimulation, but not in advanced atherosclerotic plaques, or after loading with lipid degradation products. Adenoviral transfection showed that survivin is a predominant modulator of macrophage apoptosis in atherosclerotic conditions, regardless of other IAP proteins.
	Phospholipid Transfer Protein Augments Apoptosis in THP-1–Derived Macrophages Induced by Lipolyzed Hypertriglyceridemic Plasma Andreas Wehinger, Ivan Tancevski, Wilfried Schgoer, Philipp Eller, Kathrin Hochegger, Maria Morak, Albin Hermetter, Andreas Ritsch, Josef R. Patsch, and Bernhard Foeger Arterioscler Thromb Vasc Biol. 2007;27:908-915; published online before print February 1 2007, doi:10.1161/01.ATV.0000259361.91267.8c. Abstract \| Full Text \| PDF \| Data Supplement Our study focuses on the link between postprandial lipolysis of TGRLP and vessel wall cellular toxicity. We demonstrate that human macrophages and endothelial cells show decreased viability in the presence of high lipolyzed TGRLP and that enhanced PLTP-activity augments this cytotoxicity by modulating cellular phospholipid flux and signalling events including caspase 3/7, PARP, and acid SMase.
	Identification of Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (sTWEAK) as a Possible Biomarker of Subclinical Atherosclerosis Luis M. Blanco-Colio, Jose L. Martín-Ventura, Begoña Muñóz-García, Josune Orbe, Jose A. Páramo, Jean-Baptiste Michel, Alberto Ortiz, Olivier Meilhac, and Jesús Egido Arterioscler Thromb Vasc Biol. 2007;27:916-922; published online before print February 1 2007, doi:10.1161/01.ATV.0000258972.10109.ff. Abstract \| Full Text \| PDF \| Data Supplement Using a proteomic approach, we have identified sTWEAK as a protein released in lesser amounts by atherosclerotic plaques than healthy arteries. Reduced sTWEAK plasma levels were detected in carotid atherosclerotic patients than in healthy subjects. sTWEAK levels negatively correlated with carotid IMT index. sTWEAK is a potential biomarker of atherosclerosis.
	High Frequency of a Retinoid X Receptor ${gamma}$ Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia Atsushi Nohara, Masa-aki Kawashiri, Thierry Claudel, Mihoko Mizuno, Masayuki Tsuchida, Mutsuko Takata, Shoji Katsuda, Kenji Miwa, Akihiro Inazu, Folkert Kuipers, Junji Kobayashi, Junji Koizumi, Masakazu Yamagishi, and Hiroshi Mabuchi Arterioscler Thromb Vasc Biol. 2007;27:923-928; published online before print February 1 2007, doi:10.1161/01.ATV.0000258945.76141.8a. Abstract \| Full Text \| PDF \| Data Supplement We investigated prevalence of genetic variants of several nuclear receptors in FCHL. We found a specific RXR{gamma} variant to be significantly more frequent in FCHL and to be associated with atherogenic dyslipidemia and reduced lipoprotein lipase expression. We suggest a contribution of this RXR{gamma} variant to FCHL.
	Low Plasma RANTES Levels Are an Independent Predictor of Cardiac Mortality in Patients Referred for Coronary Angiography Erdal Cavusoglu, Calvin Eng, Vineet Chopra, Luther T. Clark, David J. Pinsky, and Jonathan D. Marmur Arterioscler Thromb Vasc Biol. 2007;27:929-935; published online before print January 25 2007, doi:10.1161/01.ATV.0000258789.21585.76. Abstract \| Full Text \| PDF RANTES is a chemokine implicated in atherosclerosis. In 389 male patients undergoing coronary angiography, low baseline plasma RANTES levels were independently predictive of cardiac death. Furthermore, RANTES levels were independent predictors of cardiac mortality and MI in the non-ACS subgroup, and of cardiac mortality in the diabetic subset.
	Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men Cliona Murphy, Gajen S. Kanaganayagam, Benyu Jiang, Philip J. Chowienczyk, Rainer Zbinden, Mrinal Saha, Salman Rahman, Ajay M. Shah, Michael S. Marber, and Mark T. Kearney Arterioscler Thromb Vasc Biol. 2007;27:936-942; published online before print January 25 2007, doi:10.1161/01.ATV.0000258788.11372.d0. Abstract \| Full Text \| PDF UK South Asians have a higher incidence of coronary disease than Caucasians. 49 healthy South Asian and Caucasian men were studied. Peripheral vascular function was measured. EPC numbers and function were measured by flow-cytometry and cell culture. South Asians were more insulin resistant, had vascular dysfunction, and lower EPC numbers and function.
	Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease Ulf Landmesser, Stephan Spiekermann, Christoph Preuss, Sajoscha Sorrentino, Dieter Fischer, Costantina Manes, Maja Mueller, and Helmut Drexler Arterioscler Thromb Vasc Biol. 2007;27:943-948; published online before print January 18 2007, doi:10.1161/01.ATV.0000258415.32883.bf. Abstract \| Full Text \| PDF \| Data Supplement The present study suggests that Ang II increases endothelial cell xanthine oxidase (XO) protein levels and XO-dependent superoxide production. Importantly, endothelium-bound XO activity was markedly reduced in patients with coronary disease after AT1-receptor blocker treatment by losartan, likely representing a novel mechanism contributing to improved endothelial function after AT1-receptor blockade.
	Plasmin Induces Endothelium-Dependent Nitric Oxide–Mediated Relaxation in the Porcine Coronary Artery Tetsuhiro Fujiyoshi, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Shosuke Takahashi, and Hideo Kanaide Arterioscler Thromb Vasc Biol. 2007;27:949-954; published online before print February 1 2007, doi:10.1161/01.ATV.0000259360.33203.00. Abstract \| Full Text \| PDF \| Data Supplement Plasmin is a key enzyme in fibrinolysis, although it is known to exert cellular effects. The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.
	Thrombosis
	Thrombin Activatable Fibrinolysis Inhibitor Activation Peptide Shows Association With All Major Subtypes of Ischemic Stroke and With TAFI Gene Variation Claes Ladenvall, Ann Gils, Katarina Jood, Christian Blomstrand, Paul J. Declerck, and Christina Jern Arterioscler Thromb Vasc Biol. 2007;27:955-962; published online before print February 1 2007, doi:10.1161/01.ATV.0000259354.93789.a6. Abstract \| Full Text \| PDF \| Data Supplement We report that TAFI plasma levels are increased in overall ischemic stroke compared with controls. The association was stronger for released activation peptide than for intact TAFI. Genetic variation at the TAFI locus showed associations to TAFI levels. However, no association was observed between genetic variants and overall ischemic stroke.
	Plasma Fibrinogen, Ambulatory Blood Pressure, and Silent Cerebrovascular Lesions: The Ohasama Study Yoko Aono, Takayoshi Ohkubo, Masahiro Kikuya, Azusa Hara, Takeo Kondo, Taku Obara, Hirohito Metoki, Ryusuke Inoue, Kei Asayama, Yoriko Shintani, Junichiro Hashimoto, Kazuhito Totsune, Haruhisa Hoshi, Hiroshi Satoh, Shin-Ichi Izumi, and Yutaka Imai Arterioscler Thromb Vasc Biol. 2007;27:963-968; published online before print February 1 2007, doi:10.1161/01.ATV.0000258947.17570.38. Abstract \| Full Text \| PDF In 958 participants selected from the general Japanese population, 24-hour ambulatory blood pressure and plasma fibrinogen levels were closely and independently associated with the risk of silent cerebrovascular lesions, including white matter hyperintensity and lacunar infarct.
	Letters to the Editor
	Putative Murine Models of Plaque Rupture Erling Falk, Stephen M. Schwartz, Zorina S. Galis, and Michael E. Rosenfeld Arterioscler Thromb Vasc Biol. 2007;27:969-972, doi:10.1161/01.ATV.0000261572.33474.e0. Full Text \| PDF
	Defining and Defending Murine Models of Plaque Rupture Christopher L. Jackson Arterioscler Thromb Vasc Biol. 2007;27:973-977, doi:10.1161/01.ATV.0000261545.53586.f0. Full Text \| PDF
	Mendelian Randomization Suggests No Causal Association Between C-reactive Protein and Carotid Intima-media Thickness in the Young Finns Study Mika Kivimäki, Debbie A. Lawlor, Carita Eklund, George Davey Smith, Mikko Hurme, Terho Lehtimäki, Jorma S.A. Viikari, and Olli T. Raitakari Arterioscler Thromb Vasc Biol. 2007;27:978-979, doi:10.1161/01.ATV.0000258869.48076.14. Full Text \| PDF \| Data Supplement
	Corrections
	Correction Arterioscler Thromb Vasc Biol. 2007;27:e26, doi:10.1161/01.ATV.0000264129.47500.56. Full Text \| PDF

Spotlight

TOC Spotlight File

Volume 27, Issue 4; April 1, 2007

Editorials

Two Views on Plaque Rupture

Serum Amyloid P Component and Cardiovascular Disease: Is There a Sensible Link?

Small Is Beautiful: A Miniature Stent Model

All Oxidase Roads Lead to Angiotensin, Too

Brief Reviews

Plaque Rupture in Humans and Mice

Assessment of Unstable Atherosclerosis in Mice

Emerging Anticoagulant Drugs

Factor IXa Inhibitors as Novel Anticoagulants

Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis

Vascular Biology

Cholesterol Enhances Thrombin-Induced Release of Fibroblast Growth Factor-2 in Human Vascular Smooth Muscle Cells

Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo

Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress

Reactive Oxygen Species Activate the HIF-1 Promoter Via a Functional NFB Site

Role of the Multidrug Resistance Protein-1 in Hypertension and Vascular Dysfunction Caused by Angiotensin II

Membrane-Type Serine Protease-1/Matriptase Induces Interleukin-6 and -8 in Endothelial Cells by Activation of Protease-Activated Receptor-2: Potential Implications in Atherosclerosis

Downregulation of Bone Morphogenetic Protein 4 Expression in Coronary Arterial Endothelial Cells: Role of Shear Stress and the cAMP/Protein Kinase A Pathway

Cysteine-674 of the Sarco/Endoplasmic Reticulum Calcium ATPase Is Required for the Inhibition of Cell Migration by Nitric Oxide

Exercise Training Restores Coronary Arteriolar Dilation to NOS Activation Distal to Coronary Artery Occlusion: Role of Hydrogen Peroxide

Mineralocorticoid Receptor Activation Promotes Vascular Cell Calcification

Critical Role for Casein Kinase 2 and Phosphoinositide-3-Kinase in the Interferon-–Induced Expression of Monocyte Chemoattractant Protein-1 and Other Key Genes Implicated in Atherosclerosis

Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis

VEGFR-1 and -2 Regulate Inflammation, Myocardial Angiogenesis, and Arteriosclerosis in Chronically Rejecting Cardiac Allografts

Carbamylated Low-Density Lipoprotein Induces Monocyte Adhesion to Endothelial Cells Through Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1

Increased In-Stent Stenosis in ApoE Knockout Mice: Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting

Atherosclerosis and Lipoproteins

Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE–/– Mice

Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

Cholesteryl Ester Transfer Protein (CETP) Expression Protects Against Diet Induced Atherosclerosis in SR-BI Deficient Mice

Oral Administration of Tetrahydrobiopterin Slows the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice

Anti–LOX-1 Rescues Endothelial Function in Coronary Arterioles in Atherosclerotic ApoE Knockout Mice

A Diet-Induced Hypercholesterolemic Murine Model to Study Atherogenesis Without Obesity and Metabolic Syndrome

CD44 Regulates Vascular Gene Expression in a Proatherogenic Environment

Role of Naturally Occurring CD4+CD25+ Regulatory T Cells in Experimental Atherosclerosis

IAP Survivin Regulates Atherosclerotic Macrophage Survival

Phospholipid Transfer Protein Augments Apoptosis in THP-1–Derived Macrophages Induced by Lipolyzed Hypertriglyceridemic Plasma

Identification of Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (sTWEAK) as a Possible Biomarker of Subclinical Atherosclerosis

High Frequency of a Retinoid X Receptor Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia

Low Plasma RANTES Levels Are an Independent Predictor of Cardiac Mortality in Patients Referred for Coronary Angiography

Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men

Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease

Plasmin Induces Endothelium-Dependent Nitric Oxide–Mediated Relaxation in the Porcine Coronary Artery

Thrombosis

Thrombin Activatable Fibrinolysis Inhibitor Activation Peptide Shows Association With All Major Subtypes of Ischemic Stroke and With TAFI Gene Variation

Plasma Fibrinogen, Ambulatory Blood Pressure, and Silent Cerebrovascular Lesions: The Ohasama Study

Letters to the Editor

Putative Murine Models of Plaque Rupture

Defining and Defending Murine Models of Plaque Rupture

Mendelian Randomization Suggests No Causal Association Between C-reactive Protein and Carotid Intima-media Thickness in the Young Finns Study

Corrections

Correction

Spotlight

Reactive Oxygen Species Activate the HIF-1 ${alpha}$ Promoter Via a Functional NF ${kappa}$ B Site

Critical Role for Casein Kinase 2 and Phosphoinositide-3-Kinase in the Interferon- ${gamma}$ –Induced Expression of Monocyte Chemoattractant Protein-1 and Other Key Genes Implicated in Atherosclerosis

Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE^–/– Mice

Role of Naturally Occurring CD4⁺CD25⁺ Regulatory T Cells in Experimental Atherosclerosis

High Frequency of a Retinoid X Receptor ${gamma}$ Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia