CURRENT TRENDS IN ATHEROGENESIS Edited by Rita Rezzani Current Trends in Atherogenesis http://dx.doi.org/10.5772/56246 Edited by Rita Rezzani Contributors Agius, McGillion, Carlos Teixeira Brandt, Alexander Orekhov, Katsuri Ranganna, Ilse Van Brussel, Luigi Fabrizio Rodella, Gaia Favero, Robert Lawrence Taylor Jr., Janet Anderson, Samuel Smith, Alessandra Stacchiotti, Rita Rezzani, Zlata Flegar-Mestric, Sonja Perkov, Mirjana Marijana Kardum Paro, Vinko Vidjak, Martine Glorian Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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Publishing Process Manager Dragana Manestar Technical Editor InTech DTP team Cover InTech Design team First published February, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Current Trends in Atherogenesis , Edited by Rita Rezzani p. cm. ISBN 978-953-51-1011-8 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Chapter 1 Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection 1 Luigi Fabrizio Rodella and Gaia Favero Chapter 2 Endoplasmic Reticulum Stress in the Endothelium: A Contribution to Athero-Susceptibility 27 Alessandra Stacchiotti, Gaia Favero and Rita Rezzani Chapter 3 Dendritic Cells in Atherogenesis: From Immune Shapers to Therapeutic Targets 55 Ilse Van Brussel, Hidde Bult, Wim Martinet, Guido R.Y. De Meyer and Dorien M. Schrijvers Chapter 4 Atherogenesis: Diseases that May Affect the Natural History “Schistosomiasis and HIV Infection” 81 Carlos Teixeira Brandt, Emanuelle Tenório A. M. Godoi, André Valença, Guilherme Veras Mascena and Jocelene Tenório A. M. Godoi Chapter 5 The Evaluation of New Biomarkers of Inflammation and Angiogenesis in Peripheral Arterial Disease 97 Sonja Perkov, Mirjana Mariana Kardum Paro, Vinko Vidjak and Zlata Flegar-Meštrić Chapter 6 The Role of Cyclic 3’-5’ Adenosine Monophosphate (cAMP) in Differentiated and Trans-Differentiated Vascular Smooth Muscle Cells 121 Martine Glorian and Isabelle Limon Chapter 7 MicroRNAome of Vascular Smooth Muscle Cells: Potential for MicroRNA-Based Vascular Therapies 147 Kasturi Ranganna, Omana P. Mathew, Shirlette G. Milton and Barbara E. Hayes Chapter 8 Atherosclerosis-Susceptible and Atherosclerosis-Resistant Pigeon Aortic Smooth Muscle Cells Express Different Genes and Proteins in vitro 165 J. L. Anderson, S. C. Smith and R. L. Taylor Jr. Chapter 9 Use of Natural Products for Direct Anti-Atherosclerotic Therapy 187 Alexander N. Orekhov, Igor A. Sobenin, Alexandra A. Melnichenko, Veronika A. Myasoedova and Yuri V. Bobryshev Chapter 10 Self-Management Training for Chronic Stable Angina: Theory, Process, and Outcomes 219 M.H. McGillion, S. O’Keefe-McCarthy and S.L. Carroll Chapter 11 Attributes of Hypoxic Preconditioning Determine the Complicating Atherogenesis of Plaques 237 Lawrence M Agius ContentsVI Preface Cardiovascular diseases and atherogenesis have been and still are an important topic many scientists are working on. In the 16th century, Leonardo da Vinci had described “The narrowing of the passage of blood vessels, thickening of the coats of these vessels and hardening of arteries”. This is the first documentation of atherosclerosis, but today our understanding of atherogenesis as a process of a chronic inflammatory disease has been updated by many mechanisms such as hypercholesterolemia, dysfunction of endothelial cells, oxidation of lipoproteins and espe‐ cially oxidative stress. In particular, the endothelium is responsible for the regulation of vas‐ cular tone, the exchange of plasma and cell biomolecules, inflammation, lipid metabolism and modulation of fibrinolysis and coagulation. Endothelial cell disruption, morphological abnormalities in size and shape, susceptibility to apoptosis and abnormal release of endo‐ thelial cell-derived factors are strictly implicated in the pathogenetic mechanisms of cardio‐ vascular diseases. Growing evidence indicates that chronic and acute overproduction of oxidative stress alters endothelial cells as pivotal early event in atherogenesis. It is important to remember that drugs intake, such as statins, life style control for regulating fat intake and exercise activity must be monitored for improving cardiovascular disease in‐ cidence. In recent years a novel topic regarding antioxidant properties of some natural sub‐ stances seems to be very important for decreasing certain problems related to cardiovascular diseases and atherogenesis. This book presents the state of the art of the antioxidants in the clinical and experimental approaches in order to bring better understanding of the mechanisms and useful therapies for these diseases. We hope that it can indicate new “current trends” for identifying new aspects regarding this scientific problem involving not only anatomical and functional, but also clinical questions. Dr. Rita Rezzani University of Brescia Italy Chapter 1 Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection Luigi Fabrizio Rodella and Gaia Favero Additional information is available at the end of the chapter http://dx.doi.org/10.5772/53035 1. Introduction Cardiovascular diseases (CVDs) remain the leading cause of death in modern societies. The primary cause of dramatic clinical events of CVDs, such as unstable angina, myocardial in‐ farction and stroke, is the atherosclerotic process [1,2,3]. The pathophysiological mechanisms of atherosclerosis are complicated and the integrated picture of the disease process is not yet complete, so currently is largely investigated. It is widely recognized that oxidative stress, lipid deposition, inflammation, Vascular smooth muscle cells (VSMCs) differentiation and endothelial dysfunction play a critical role in the formation, progression and eventually rupture of the atherosclerotic plaque [4]. Multiple risk factors have been associated with the development of atherosclerotic lesions; these include diabetes mellitus, hypertension, obesity and tobacco smoking. The risk factors are influenced by genetic predisposition, but also by environmental factors, particularly diet. Moreover, ag‐ ing promotes physiological changes, such as oxidative stress, inflammation and endothelial dysfunction strictly associated with the pathophysiology of atherosclerosis [5]. The common belief that signs of atherosclerosis and CVDs are clinically relevant only dur‐ ing adult and elderly age is gradually changing, increasing evidence supports that athero‐ genesis is initiated in childhood [6]. Low-density lipoproteins (LDL) are crucial to the development of atherosclerotic lesions, whereas high-density lipoproteins (HDL) are inhibitors of the process, primarily through the process of reverse cholesterol transport [4,7]. Dysfunctional lipid homeostasis plays a central role in the initiation and progression of atherosclerotic lesions. Oxidized-LDL (ox- LDL) induces endothelial dysfunction with focal inflammation which causes increased ex‐ pression of atherogenic signaling molecules that promote the adhesion of monocytes and T © 2013 Fabrizio Rodella and Favero; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. lymphocytes to the arterial endothelium and their penetration into the intima. Early stages of plaque development involve endothelial activation induced by inflammatory cytokines, ox-LDL and/or changes in endothelial shear stress [8,9]. The monocyte-derived macrophag‐ es, by taking up ox-LDL, become foam cells, which are typical cellular elements of the fatty streak, the earliest detectable atherosclerotic lesion [10]. After initial injury, different cell types, including endothelial cells, platelets and inflammato‐ ry cells release growth factors and cytokines that induce multiple effects: oxidative stress, inflammation, VSMCs differentiation from the contractile state to the active synthetic state and then proliferate and migrate in the subendothelial space [11,12]. Inflammatory cell accu‐ mulation, migration and proliferation of VSMCs, as well as the formation of fibrous tissue, lead to the enlargement and restructuring of the lesion, with the formation of an evident fi‐ brous cap and other vascular morphological changes [2,13]. Atherosclerotic plaques result from the progressive accumulation of cholesterol and lipids in oxidized forms, extracellular matrix material and inflammatory cells [14]. In fact, atherosclerosis manifests itself histologi‐ cally as an arterial lesions known as plaques, which have been extensively characterized: plaques contain a central lipid core that is most often hypocellular and may include crystals of cholesterol that have formed in the foam cells. The lipid core is separated from the arterial lumen by a fibrous cap and myeloproliferative tissue that consists of extracellular matrix and VSMCs. Advanced lesions can grow sufficiently large to block blood flow and so devel‐ op an acute occlusion due to the formation of thrombus or blood clot resulting in the impor‐ tant and severe cardiovascular clinical events [2,10]. Figure 1. Main vascular alterations observed during atherogenesis. LDL: low density lipoprotein; HDL: high density lip‐ oprotein. Current Trends in Atherogenesis2 [...]... epigallocatechin gallate, being the most abundant catechin (48–55%), followed by epi‐ 11 12 Current Trends in Atherogenesis gallocatechin (9–12%), epicatechin gallate (9–12%) and epicatechin (5–7%) [42] The catechin content of green tea depends on several factors including how the leaves are processed be‐ fore drying, preparation of the infusion and decaffeination, as well as the form in which it is... is distributed in the market (instant preparations, iced and ready-to-drink teas have been shown to contain fewer catechins) [43] When tea leaves are rolled or broken during indus‐ try manufacture, catechins come in contact with polyphenol oxidase, resulting in their oxi‐ dation and the formation of flavanol dimers and polymers known as theaflavins and thearubigins [44] Tea leaves destined to become... requirement of vitamin C and is high in polyphenol compounds The pomegranate plant contains alkaloids, 13 14 Current Trends in Atherogenesis mannite, ellagic acid and gallic acid and the bark and rind contain various tannins The pol‐ yphenols in pomegranate are believed to provide the anti-oxidant activity and protect LDL against cell-mediated oxidation directly by interaction with the LDL [49] In fact, the... may contain aflatoxin, a potent hepatocarcinogen; thus, it should be used cautiously by patients who have hepatic dysfunction or who are taking other hepatotoxic agents Pomegranate may also increase the risk for rhabdomyolysis during statin therapy, as a result of intestinal CYP3A4 inhibition and increased absorption of active drugs [49] 10 Wine The last two decades have seen renewed interest in the... when added in combination [74] Moreover, 6-hydroxymelatonin, the main in vivo metabolite of melatonin, and its precursor, N-acetyl-5-hydroxytryptamine, were potent in reducing in vitro LDL peroxidation The abili‐ ty of the parent molecule melatonin as well as its metabolites to function in radical detoxifi‐ cation greatly increases its ability to limit oxidative abuse at many levels within cells [9]... vita‐ min E in hypercholesterolemic patients and/or chronic smokers increase levels of autoanti‐ bodies against ox-LDL There is also a quite convincing evidence from in vitro studies that vitamin C strongly inhibits LDL oxidation [27] It is important to underline that there are no definite recommendations on the dose and du‐ ration of supplementation with vitamins in human Although, high dietary intake... Toll-like receptors (TLRs), that in turn at‐ tract leukocytes adhesion in the intima layer Mainly TLR 2 and TLR4 are active in mouse in the progression of atherosclerosis and their signals stimulate a downstream adaptor mole‐ cule, called Toll/IL-1 receptor domain-related adaptor protein that induces interferon or TRIF Indeed also in human vascular tree, by immunostaining and mRNA survey TLR2 and TLR4... also affect indirectly the redox status by increasing the capacity of en‐ dogenous anti-oxidants or by inhibiting enzymatic systems involved in ROS formation [36] The free-radical scavenging activity of many polyphenols has been reported to be much stronger than that of vitamin C, vitamin E or glutathione, the major anti-oxidants present in the body In spite of their potent protective effects in the development... interest in the health benefits of wine, as documented by increasing research and several epidemiologic observations showing that moderate wine drinkers have lower cardiovascular mortality rates than heavy drinkers or teetotalers Most of the beneficial effects of wine against CVDs have been attributed to the presence in red wine of resveratrol and other polyphenols Wines contain polyphenolic compounds that... one hand, due to its richness in oleic acid and, on the other hand, due to its minor components of the olive oil particularly 15 16 Current Trends in Atherogenesis the phenolic compounds The phenolic content in virgin olive oil could reduce the lipid oxi‐ dation and inhibit platelet-induced aggregation [53] Moreover, olive oil minor components have also been involved in the anti-oxidant activity of . CURRENT TRENDS IN ATHEROGENESIS Edited by Rita Rezzani Current Trends in Atherogenesis http://dx.doi.org/10.5772/56246 Edited. radical scaveng‐ ing activity [27,40]. Current Trends in Atherogenesis1 0 Since the evidence of therapeutic effects of dietary flavinoids continues to accumulate,