Sauer / Shah / Laurindo Studies on Cardiovascular Disorders

1. Auflage 2010
ISBN: 978-1-60761-600-9
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 590 Seiten

Reihe: Oxidative Stress in Applied Basic Research and Clinical Practice

This collection of articles on oxidative stress in clinical practice surveys essential current research in what is a rapidly evolving field. As well as giving the reader a mechanistic overview of how oxidative stress affects cardiovascular disease, it analyzes the potential of a number of therapeutic options that target these pathways. Understanding the complexity of the cellular redox system could lead to the development of better targeted interventions that facilitate patient recovery. Even as large-scale clinical trials of so-called 'simple' antioxidant approaches such as vitamins C and E show that significant benefits for cardiovascular patients remain elusive, Studies on Cardiovascular Disorders demonstrates that such approaches are too simplistic. Beginning with a summary of redox signaling models that could induce the progression of redox-associated cardiovascular disorders, the volume moves on to examine redox-mediated protein modification under physiological and pathophysiological conditions. It provides an outline of the signaling pathways in cardiovascular development during embryogenesis, and what impact these might have in the differentiation process of resident cardiac and blastocyst derived stem cells. Further chapters detail our current knowledge of the influence the sensory nervous system exerts on the cardiovascular system, and the paradoxical role of mitochondria-derived ROS in cardiac protection. In all, almost 30 contributions cover issues as diverse as the antioxidant properties of statins in the heart and the oxidative risk factors for cardiovascular disease in women. A range of medical practitioners will find the contents of Studies on Cardiovascular Disorders provides illuminating insight into the Janus-faced role of ROS in the cardiovascular system.

Autoren/Hrsg.

Sauer, Heinrich

Shah, Ajay M.

Laurindo, Francisco R. M.

Inhaltsverzeichnis

1;Preface;5
2;Contents;9
3;Contributors;12
4;1 The Evolving Concept of Oxidative Stress;17
4.1;1.1 A Brief Historical Note and Some Definitions;18
4.2;1.2 Molecular Damage by Free Radicals and Oxidant Species;19
4.3;1.3 The Redox Signaling Concept;21
4.4;1.4 Reactivity of Thiols: A Chemical Route for Redox-Dependent Messages;23
4.4.1;1.4.1 Thiol Oxidation Pathways;23
4.4.2;1.4.2 Mechanism for Thiol-Mediated Signal Transduction;27
4.5;1.5 The Evolving Characteristic of Redox Signaling Models: Critical Analysis;29
4.6;1.6 Compartmentalization: One of Natures Solutions for Redox Signaling Specificity and Robustness;33
4.7;1.7 Redox Modularity: A Systems BiologyBased Version of Compartmentalization;34
4.8;1.8 Oxidative Stress as Collateral Supra-Modular Signaling: A Proposal;36
4.9;1.9 Intermediate States of Redox Signaling vs. Oxidative Stress;37
4.10;1.10 Reduction-Dependent Signaling and Reductive Stress;38
4.11;1.11 Integration of Oxidative Stress at the Cellular Level: Convergence with Other Types of Stress;39
4.12;1.12 Assessment of Disrupted Signaling Due to Oxidative Stress: Problems and Perspectives;40
4.12.1;1.12.1 Approaches for Reactive Species Detection and Oxidative Stress Measurement;41
4.12.2;1.12.2 Approaches for Redox State Measurement;44
4.12.3;1.12.3 How to Choose a Particular Method for Detection of Reactive Species or Oxidative Stress;45
4.13;1.13 Redefining Antioxidants and Antioxidant Therapy in a Redox Signaling Scenario;46
4.14;1.14 Concluding Remarks;46
4.15;References;47
5;2 Mechanisms of Redox Signaling in Cardiovascular Disease;58
5.1;2.1 Overview of Cardiovascular Disease;58
5.2;2.2 Oxidative StressA Recurrent Hallmark of Cardiovascular Pathologies;59
5.3;2.3 Nondeleterious Roles for Oxidants;60
5.4;2.4 Cellular Oxidants;61
5.5;2.5 Protein Oxidation Involved in Redox Signaling;62
5.6;2.6 Techniques for Monitoring Thiol Redox State;65
5.7;2.7 Proteins in the Cardiovascular System That Are Thiol Redox Modulated;66
5.8;2.8 Conclusions;67
5.9;References;70
6;3 Reactive Oxygen and Nitrogen Species in Cardiovascular Differentiation of Stem Cells;76
6.1;3.1 Introduction;77
6.2;3.2 Oxygen and ROS Generation During Embryogenesis;77
6.3;3.3 Oxidative Stress During Myocardial InfarctionA Potential Stimulus for Stem Cell Activation;78
6.4;3.4 Stem Cells Within the Heart and Potential Redox-Regulated Signaling Pathway Involved in Stem Cell Proliferation and Specification;79
6.5;3.5 Impact of Redox-Regulated Pro-angiogenic Signals During Cardiac Infarction;82
6.6;3.6 Redox-Regulated Pathways Involved in Mobilization of Stem Cells from the Bone Marrow;83
6.7;3.7 NO and ROS in EPC Mobilization and Function;85
6.8;3.8 ROS and NO Generation in Bone MarrowDerived Stem Cells;88
6.9;3.9 ROS and NO in Cardiovascular Differentiation of Embryonic Stem Cells;89
6.10;3.10 Summary and Conclusions;92
6.11;References ;92
7;4 Reactive Oxygen Species (ROS) and the Sensory Neurovascular Component;101
7.1;4.1 Introduction;101
7.2;4.2 The Sensory Neurogenic Component and Vascular Innervation;102
7.2.1;4.2.1 Nerve Activating Mechanisms and Cardiovascular Consequences of Neuropeptide Action;102
7.3;4.3 ROS and Localization Within Sensory Nerves;103
7.4;4.4 Vascular Effects of ROS;104
7.5;4.5 Neuropeptides and Interactions with Vascular-Derived ROS;106
7.6;4.6 CGRP;106
7.6.1;4.6.1 CGRP and Protection Against Oxidative Stress as a Consequence of Vasodilator Networks;107
7.6.2;4.6.2 CGRP and Protection via Vasodilator-Independent Mechanisms Against ROS-Mediated Vascular Injury;107
7.6.3;4.6.3 Substance P;108
7.6.4;4.6.4 Influence of Vascular-Derived ROS on Substance P--Induced Vasodilatation;108
7.6.5;4.6.5 Influence of Substance P on Inflammatory ROS Production;109
7.7;4.7 TRP Receptor and Localization on Sensory Nerves;109
7.7.1;4.7.1 TRPV1 Receptors and Links with ROS;111
7.7.2;4.7.2 H2O2 as a TRPA1 Receptor Agonist ;112
7.7.3;4.7.3 Products of Oxidative Stress as TRPA1 Receptor Agonists;114
7.8;4.8 Conclusions and Therapeutic Implications;115
7.9;References;115
8;5 Mitochondrial Reactive Oxygen Species in Myocardial Pre- and Postconditioning;122
8.1;5.1 Mitochondrial ROS Generation in the Heart;122
8.2;5.2 Regulation of Mitochondrial ROS Generation by Mild Uncoupling Pathways;123
8.3;5.3 Mitochondrial Permeability Transition: A Cell DeathInducing Consequence of Mitochondrial Oxidative Stress;125
8.4;5.4 Preconditioning and Mitochondrial Redox Signaling;126
8.5;5.5 Postconditioning and Mitochondrial Redox Signaling;129
8.6;5.6 Concluding Remarks;130
8.7;References;130
9;6 Coenzyme Q9/Q10 and the Healthy Heart;137
9.1;6.1 Introduction;137
9.2;6.2 A Quick Look Back;138
9.3;6.3 Natural Occurrence and Distribution;140
9.4;6.4 The Biochemical Background;141
9.5;6.5 Physiological Effects;141
9.6;6.6 Pharmacokinetics;142
9.7;6.7 Cardioprotective Effects;143
9.7.1;6.7.1 Heart Failure;144
9.7.2;6.7.2 Atherosclerosis;145
9.7.3;6.7.3 Hypertension;145
9.7.4;6.7.4 Cardiac and Vascular Surgery;145
9.7.5;6.7.5 Pharmacological Preconditioning Effects;146
9.8;6.8 Conclusion;147
9.9;References;147
10;7 Oxidative and Proteolytic Stress in Homocysteine-Associated Cardiovascular Diseases;151
10.1;7.1 Introduction;151
10.2;7.2 HCY Mechanism of Oxidative and Nitrosative Stress;154
10.3;7.3 HHCY, Oxidative Stress, and Myocyte Dysfunction;155
10.4;7.4 H2S Hypothesis of Cardioprotection in HHCY ;156
10.5;7.5 Proliferation and Maintenance of Resident Cardiac Stem Cell, MMP/TIMP Levels, and FoxO Transcription Factor;157
10.6;References;159
11;8 Functional Studies of NADPH Oxidases in Human Vasculature;161
11.1;8.1 Introduction;162
11.2;8.2 Functional Studies of Oxidative Stress in Human Vasculature;162
11.2.1;8.2.1 Ex Vivo Studies;162
11.2.2;8.2.2 In Vivo Studies;164
11.3;8.3 Role of Reactive Oxygen Species in the Regulation of Endothelial Function in Human Vasculature;164
11.4;8.4 Vessel Wall Layers Contributing to Total Vascular Superoxide;166
11.5;8.5 New Functional Hypothesis of Oxidative Stress;167
11.6;8.6 NADPH Oxidases as Main Sources of Reactive Oxygen Species in Human Vasculature;168
11.6.1;8.6.1 Regulation of NADPH Oxidases in Human Vasculature;171
11.6.2;8.6.2 Central Role of NADPH Oxidases in Regulating Oxidative Stress;172
11.7;8.7 Risk Factors for Atherosclerosis and Vascular NADPH Oxidases;172
11.8;8.8 NADPH Oxidases in Bypass Graft Conduit Vessel Disease and Dysfunction;173
11.9;8.9 Functional Studies of Genetic Regulation of NADPH Oxidases;174
11.10;8.10 Conclusions;174
11.11;References;175
12;9 Relationship of the CYBA Gene Polymorphismswith Oxidative Stress and Cardiovascular Risk;180
12.1;9.1 Introduction;181
12.2;9.2 The NADPH Oxidase System;181
12.3;9.3 p22 phox Genetic Variants and Cardiovascular Disease;182
12.3.1;9.3.1 C242T Polymorphism;183
12.3.2;9.3.2 A640G Polymorphism;187
12.3.3;9.3.3 -930 A/G Polymorphism;187
12.3.4;9.3.4 -675 A/T Polymorphism;189
12.3.5;9.3.5 Other CYBA Polymorphisms;189
12.4;9.4 Genetic and Environmental Interactions;190
12.5;9.5 Summary and Conclusions;192
12.6;References;193
13;10 Redox-Related Genetic Markers of CardiovascularDiseases;198
13.1;10.1 Introduction;198
13.2;10.2 Phenotypic Quality;199
13.3;10.3 Strategies to Unravel the Genetics of Redox-Related Diseases;201
13.3.1;10.3.1 Candidate Gene Approach;201
13.3.1.1;10.3.1.1 NADPH Oxidase;201
13.3.1.2;10.3.1.2 Superoxide Dismutase;203
13.3.1.3;10.3.1.3 Other Redox-Related Candidate Genes;204
13.3.2;10.3.2 Rodent Models and Translational Approaches;205
13.3.3;10.3.3 Genome-Wide Association Studies;207
13.3.4;10.3.4 Mitochondria;208
13.4;10.4 Interactions Between Genes and Environment;209
13.4.1;10.4.1 Antioxidant Therapy;209
13.4.2;10.4.2 Smoking;210
13.4.3;10.4.3 Medication and Pharmacogenetics;210
13.5;10.5 Regulation of Transcription;211
13.6;10.6 Summary and Conclusions;211
13.7;References;212
14;11 NADPH Oxidases and Blood-Brain Barrier Dysfunctionin Stroke;221
14.1;11.1 Introduction;221
14.2;11.2 The Clinical Setting of Stroke;222
14.3;11.3 Reactive Oxygen Species in Ischemic Brain Injury;223
14.4;11.4 NADPH Oxidases in the Central Nervous System;223
14.5;11.5 The Role of NADPH Oxidases in Ischemic Stroke;225
14.5.1;11.5.1 NADPH Oxidases in Ischemia/Reperfusion Outside of the Brain;225
14.5.2;11.5.2 Cerebral NADPH Oxidases and Ischemic Brain Injury;226
14.6;11.6 The Blood-Brain Barrier;227
14.6.1;11.6.1 Structural Components of the Blood-Brain Barrier;227
14.6.2;11.6.2 In Vivo Regulation of the Blood-Brain Barrier;228
14.6.3;11.6.3 Blood-Brain Barrier Dysfunction in Stroke;229
14.6.4;11.6.4 Mechanisms of Blood-Brain Barrier Opening;230
14.7;11.7 The Role of NADPH Oxidases in Blood-Brain Barrier Dysfunction;231
14.8;11.8 Summary and Conclusion;234
14.9;References;234
15;12 Smoking-Induced Oxidative Stress in the Pathogenesisof Cardiovascular Diseases;241
15.1;12.1 Introduction;242
15.2;12.2 Smoking as a Source for Oxidative Stress in the Cardiovascular System;242
15.2.1;12.2.1 Generation of Oxidants and Radicals by Combustion of Cigarette Constituents;242
15.2.2;12.2.2 Secondary Generation of Oxidants and Radicals by Cigarette Smoke in the Cardiovascular System;243
15.2.2.1;12.2.2.1 Secondary Oxidative Stress in the Vessel Wall by Smoking-Caused Inflammation;243
15.2.2.2;12.2.2.2 Oxidative Stress by Smoking-Caused Reduction of Physiological Antioxidants;244
15.2.2.3;12.2.2.3 Smoking-Mediated Modulation of Gene Expression as a Source for Cardiovascular Oxidative Stress;245
15.2.2.4;12.2.2.4 Cigarette Smoke--Contained Metals, a Source for Chronic Oxidative Stress in the Vessel Wall;246
15.3;12.3 Smoking-Caused Oxidative Stress as a Pathophysiological Factor in Cardiovascular Disease Initiation and Progression;246
15.3.1;12.3.1 The Role of Smoking-Caused Oxidative Stress in CVD Initiation;246
15.3.1.1;12.3.1.1 Impact of Smoking on Endothelial Function;246
15.3.1.2;12.3.1.2 Smoking and the Autoimmune Hypothesis of Atherosclerosis;247
15.3.1.3;12.3.1.3 Smoking and Lipid Oxidation;247
15.3.2;12.3.2 The Role of Smoking-Caused Oxidative Stress in CVD Progression;248
15.3.2.1;12.3.2.1 Smoking-Mediated Oxidative Stress and Inflammation in CVD Progression;248
15.3.2.2;12.3.2.2 Smoking-Induced Vascular Aging as a CVD-Promoting Factor;249
15.3.2.3;12.3.2.3 Smoking, Oxidative Stress, and Thrombogenesis;249
15.3.3;12.3.3 Oxidative Stress--Independent Mechanisms in CVD Initiation and Progression;249
15.3.3.1;12.3.3.1 Nonoxidative Smoke Chemicals and CVD Initiation;249
15.3.3.2;12.3.3.2 Smoking, Collagen Synthesis, and Plaque Stability;250
15.4;12.4 Summary and Conclusions;251
15.5;References;251
16;13 Oxidative Stress in Vascular Aging;254
16.1;13.1 Introduction;254
16.2;13.2 Oxidative Stress in Vascular Aging: Role of NAD(P)H Oxidases;255
16.3;13.3 Role of Mitochondrial Oxidative Stress in Arterial Aging;256
16.4;13.4 Low-Grade Vascular Inflammation During Aging: Role of Oxidative Stress;259
16.5;13.5 Caloric Restriction Attenuates Vascular Oxidative Stress in Aging;260
16.6;13.6 Attenuation of Age-Related Vascular Oxidative Stress by the Caloric Restriction Mimetic Resveratrol;262
16.7;13.7 Conclusions;263
16.8;References;263
17;14 Oxidative Stress and Cardiovascular Diseasein Diabetes Mellitus;271
17.1;14.1 Introduction;271
17.2;14.2 Enzymatic Sources of Reactive Oxygen Species in Diabetes;272
17.2.1;14.2.1 DAG-PKC Activation;272
17.2.2;14.2.2 NADPH Oxidase;274
17.2.3;14.2.3 Cellular Respiration;274
17.2.4;14.2.4 Oxidative Stress and Advanced Glycation End Products;274
17.2.5;14.2.5 Oxidative Stress and the Polyol Pathway;276
17.3;14.3 Role of Reactive Oxygen Species in the Cardiovascular Consequences of Diabetes;277
17.3.1;14.3.1 Endothelial Dysfunction;278
17.3.2;14.3.2 Diabetes and Hypertension;280
17.3.3;14.3.3 Diabetes and Atherosclerosis;281
17.3.4;14.3.4 Diabetes and Thrombosis;282
17.3.5;14.3.5 Diabetic Cardiomyopathy;282
17.3.6;14.3.6 Arrhythmia;283
17.4;14.4 Summary;284
17.5;References;284
18;15 Reactive Oxygen Species, Oxidative Stress, and Hypertension;288
18.1;15.1 Introduction;289
18.2;15.2 Biology of ROS;290
18.3;15.3 Production and Metabolism of ROS in the Cardiovascular System;291
18.3.1;15.3.1 Xanthine Oxidase;291
18.3.2;15.3.2 Uncoupled Nitric Oxide Synthase;292
18.3.3;15.3.3 Mitochondrial Respiratory Enzymes;293
18.3.4;15.3.4 ROS-Generating Nox Family NAD(P)H Oxidases;294
18.3.4.1;15.3.4.1 Distribution of Noxes in the Vascular Wall;296
18.3.4.2;15.3.4.2 Regulation of Noxes;296
18.4;15.4 Protecting Against Oxidative Stress: Antioxidant Defenses;297
18.5;15.5 ROS and Vascular (Patho)Biology in Hypertension;298
18.6;15.6 Oxidative Stress in Experimental Hypertension;299
18.7;15.7 Oxidative Stress and Clinical Hypertension;301
18.8;15.8 Antioxidant Therapy and Human Hypertension;303
18.9;15.9 Other Possible Strategies to Reduce Oxidative Stress;304
18.10;15.10 Conclusions;305
18.11;References;306
19;16 Peripartum Cardiomyopathy: Role of STAT-3 and Reactive Oxygen Species;323
19.1;16.1 Introduction;324
19.2;16.2 Oxidative Stress and Antioxidative Defense During Pregnancy and Postpartum;325
19.2.1;16.2.1 Oxidative Stress Factors;325
19.2.2;16.2.2 Antioxidant Capacity;325
19.2.3;16.2.3 Summary;326
19.3;16.3 Peripartum Cardiomyopathy (PPCM);327
19.4;16.4 Potential Risk Factors for PPCM;327
19.4.1;16.4.1 Infectious Agents;327
19.4.2;16.4.2 Autoimmune Responses;328
19.4.3;16.4.3 Preeclampsia;328
19.4.3.1;16.4.3.1 Oxidative Modification of Lipids;329
19.4.3.2;16.4.3.2 Activation of the Immune System by Oxidative Stress Mechanisms;329
19.4.3.3;16.4.3.3 Asymmetric Dimethylarginine (ADMA);330
19.5;16.5 Mechanistic Insights into the Pathophysiology of Peripartum Cardiomyopathy;331
19.5.1;16.5.1 The Estrogen-PI3-Akt Connection;331
19.5.2;16.5.2 STAT3, the Guardian of Postpartum Hearts;331
19.5.3;16.5.3 STAT3 and Antioxidant Pathways in the Postpartum Heart: An Important Role for MnSOD;332
19.5.4;16.5.4 Oxidative Stress and High Prolactin Levels: A Detrimental Combination;333
19.5.5;16.5.5 Impact of the 16-kDa Prolactin on the Cardiovascular System;334
19.6;16.6 How Relevant is the STAT3Oxidative StressProlactin Hypothesis for Human PPCM;335
19.6.1;16.6.1 Gene Polymorphisms and Dysregulation of STAT3 Signaling Pathways in Human PPCM;335
19.6.2;16.6.2 Evidence for the Oxidative Stress--Prolactin Hypothesis in Human PPCM;336
19.6.2.1;16.6.2.1 Oxidative Stress and Inflammation;336
19.6.2.2;16.6.2.2 Cathepsin D, Prolactin Cleavage, and Bromocriptine;336
19.6.2.3;16.6.2.3 16-kDa Prolactin in Prepartum Cardiovascular Disease;337
19.6.2.4;16.6.2.4 Summary;337
19.6.3;16.6.3 Prolactin, Bromocriptine, and the Risk for Thrombosis;337
19.7;16.7 Summary and Conclusions;338
19.8;References;339
20;17 Oxidative Stress and Inflammation after CoronaryAngiography;344
20.1;17.1 Introduction;344
20.2;17.2 Oxidative Stress During Percutaneous Coronary Intervention;345
20.3;17.3 Antioxidant Approaches in Clinical Practice;345
20.3.1;17.3.1 Myeloperoxidase (MPO) as a Biomarker of Oxidative Stress in Cardiovascular Disease;346
20.3.2;17.3.2 Role of PMNLs;349
20.4;17.4 Summary;350
20.5;References;351
21;18 Oxidative Stress in Cardiac Transplantation;354
21.1;18.1 Introduction;354
21.2;18.2 Oxidative Stress in Human Cardiac Transplantation;355
21.3;18.3 Rationale for Antioxidant/Vitamin Intervention;357
21.4;18.4 Donor Heart Preservation, Ischemia-Reperfusion Injury, and Oxidative Stress;358
21.5;18.5 Specific Role of Superoxide;359
21.5.1;18.5.1 Superoxide in Cardiac Transplantation;359
21.5.2;18.5.2 Superoxide in Cardiac Rejection;359
21.5.3;18.5.3 Direct Measures of Superoxide in Cardiac Grafts;360
21.6;18.6 NADPH Oxidase in Cardiac Transplantation;363
21.7;18.7 Apoptosis and Oxidative Stress in Cardiac Transplantation;363
21.7.1;18.7.1 Role of Ischemia-Reperfusion--Induced Apoptosis;363
21.7.2;18.7.2 Role of Intrinsic vs. Extrinsic Pathways of Ischemia-Reperfusion--Induced Apoptosis;364
21.7.3;18.7.3 Relationship of Oxidative Stress and Apoptosis in Cardiac Rejection;364
21.8;18.8 Reactive Oxygen Species and Immune Suppression;365
21.8.1;18.8.1 Cyclosporine-Induced Production of Superoxide;365
21.8.2;18.8.2 Cyclosporine-Induced Oxidative Stress;366
21.8.3;18.8.3 Reactive Oxygen and Other Immunosuppressant Agents;366
21.8.4;18.8.4 Immunosuppression, Cytomegalovirus, and Oxidative Stress;367
21.9;18.9 The Triad of the Renin-Angiotensin System, Tgf-, and Oxidative Stress in Transplantation;368
21.9.1;18.9.1 Effect of Angiotensin II on the Heart;368
21.9.2;18.9.2 TGF-, Oxidative Stress, and Cardiac Transplantation;368
21.10;References;370
22;19 Oxidative Stress and Atrial Fibrillation;377
22.1;19.1 Introduction;377
22.2;19.2 The Electrical Basis of AF;380
22.3;19.3 The Central Role of Myocardial Fibrosis, Inflammation, and Oxidative Stress in AF;381
22.4;19.4 Biomarkers and Cellular Mechanisms of Oxidative Stress in AF;382
22.5;19.5 Oxidative Stress and Thromboembolism in AF;385
22.6;19.6 Therapeutic Implications of Increased ROS in AF;386
22.7;19.7 Conclusion;387
22.8;References;387
23;20 Oxidative Stress and the Antioxidative Capacityin Myocardial Infarction;392
23.1;20.1 Introduction;392
23.2;20.2 Cardiac Oxidative Stress and Antioxidant Capacity;393
23.2.1;20.2.1 Reactive Oxygen Species Production;393
23.2.2;20.2.2 Occurrence of Cardiac Oxidative Stress Following Myocardial Infarction;394
23.3;20.3 Oxidative Stress and Cardiac Remodeling and Dysfunction;394
23.3.1;20.3.1 Cardiomyocyte Apoptosis in the Infarcted Heart;394
23.3.2;20.3.2 Oxidative Stress and Cardiac Inflammatory Response in the Infarcted Heart;398
23.3.3;20.3.3 Oxidative Stress and Cardiac Fibrosis Following Infarction;399
23.3.4;20.3.4 Oxidative Stress and Cardiac Hypertrophy Following Infarction;400
23.3.5;20.3.5 Oxidative Stress and Heart Failure;401
23.4;20.4 Summary;402
23.5;References;402
24;21 Oxidative Stress and Redox Signalling in CardiacRemodelling;407
24.1;21.1 Introduction;408
24.2;21.2 ROS, Oxidative Stress, and Redox Signalling;408
24.3;21.3 Cardiac Sources of ROS;409
24.4;21.4 ROS and Cardiac Hypertrophy;411
24.5;21.5 Extracellular Matrix Modification and Interstitial Fibrosis;413
24.6;21.6 ROS and Apoptosis;415
24.7;21.7 ROS, Contractile Dysfunction, and Energetics;416
24.8;21.8 Therapeutic Intervention;417
24.9;21.9 Conclusions;418
24.10;References;419
25;22 Oxidative Stress and Cardiovascular Fibrosis;427
25.1;22.1 Introduction;427
25.2;22.2 Congestive Heart Failure: Epidemiology and Risk Factors;428
25.3;22.3 Oxidative Stress in the Initiation/Progression of Vascular Disease;430
25.4;22.4 Oxidative Stress Pathways in Cardiovascular Disease;431
25.5;22.5 Biomarkers of Oxidative Stress Pathways;434
25.6;22.6 NOX Enzymes and Cardiovascular Fibrosis;436
25.7;22.7 Therapeutic Implications for Cardiovascular Fibrosis;437
25.8;References;438
26;23 Oxidative Risk Factors for Cardiovascular Disease in Women;444
26.1;23.1 Introduction;445
26.2;23.2 Role of Lipid Peroxidation in the Epidemiology of CVD in Women;445
26.3;23.3 Summary;449
26.4;References;450
27;24 Protective Effects of Food on Cardiovascular Diseases;455
27.1;24.1 Oxidative Stress;455
27.2;24.2 L-arginine;457
27.3;24.3 Lycopene;457
27.4;24.4 Phenols and Polyphenols;459
27.5;24.5 Dietary Fiber;462
27.6;24.6 Fatty Acids;463
27.7;24.7 Phytosterols;464
27.8;24.8 Ethanol and Nonethanolic Components of Wine;464
27.9;References;465
28;25 Novel Synthetic Antioxidants and Nitrated Lipids: From Physiology to Therapeutic Implications;472
28.1;25.1 Introduction;472
28.2;25.2 Natural Antioxidants and Prevention of Cardiovascular Disease;473
28.2.1;25.2.1 Introduction to Vitamin E;473
28.2.2;25.2.2 Randomized and Placebo-Controlled Studies for Primary and Secondary Prevention of Atherosclerosis;477
28.3;25.3 Synthetic Antioxidants Represent an Exciting Novel Strategy to Prevent Cardiovascular Disease;480
28.4;25.4 Nitrolipids;489
28.5;25.5 Conclusions;490
28.6;References;490
29;26 Thioredoxin in the Cardiovascular SystemTowards a Thioredoxin-Based Antioxidative Therapy;498
29.1;26.1 Introduction;498
29.2;26.2 Actions of TRX;499
29.2.1;26.2.1 Antioxidant Properties;499
29.2.2;26.2.2 Signaling;500
29.2.3;26.2.3 Transcription;501
29.2.4;26.2.4 Survival;502
29.3;26.3 Regulation of TRX Activity;503
29.3.1;26.3.1 Oxidation;503
29.3.2;26.3.2 Nitrosylation;503
29.3.3;26.3.3 Glutathionylation;504
29.3.4;26.3.4 Nitration;505
29.4;26.4 Perturbation of TRX in Vascular Disease;505
29.4.1;26.4.1 Plasma Levels;505
29.4.2;26.4.2 Expression;506
29.5;26.5 Expression and Actions of a TRX Inhibitor;506
29.5.1;26.5.1 TRX-Interacting Protein;506
29.6;26.6 Genetic Manipultion of TRX Expression;507
29.6.1;26.6.1 Transgenic Mice;507
29.7;26.7 Therapeutic Use of TRX;508
29.8;26.8 Summary and Conclusions;509
29.9;References;510
30;27 The Protective Effect of Melatonin on the Heart;516
30.1;27.1 Melatonin and the Heart;516
30.2;27.2 Melatonin and Ischaemia/Reperfusion Injury;518
30.3;27.3 Role of the Melatonin Receptors in Cardioprotection;519
30.4;27.4 Antiadrenergic Actions of Melatonin;521
30.5;27.5 Melatonin and Mitochondria;522
30.6;27.6 Melatonin and Intracellular Ca 2 Handling;524
30.7;27.7 Reversal of Harmful Effects of Clinically Used Drugs;525
30.8;27.8 Melatonin as Cardioprotective Agent in Humans;526
30.9;References;527
31;28 Exercise-Induced Cardioprotection: Overview with an Emphasis on the Role of Antioxidants;534
31.1;28.1 Introduction;534
31.2;28.2 Principles of Myocardial IR Injury;535
31.3;28.3 Oxidative Stress in Myocardial IR Injury;536
31.3.1;28.3.1 Calcium Regulation, Proteolysis, Membrane Integrity, and Inflammation;537
31.4;28.4 Exercise-Induced Protection Against Myocardial IR Injury: Overview of Putative Mechanisms;539
31.4.1;28.4.1 Coronary Circulation;539
31.4.2;28.4.2 Myocardial Heat Shock Proteins;539
31.4.3;28.4.3 Regulation of Calcium;542
31.4.4;28.4.4 ATP-Sensitive Potassium Channels and Protein Kinase C;542
31.5;28.5 Role of Antioxidants in Exercise-Induced Cardioprotection;543
31.5.1;28.5.1 An Introduction to Intrinsic Defenses;543
31.5.2;28.5.2 Exercise, Enzymatic Antioxidants, and Cardioprotection;544
31.5.3;28.5.3 Exercise and Nonenzymatic Compounds That Scavenge ROS;547
31.6;28.6 Oxidative Stress Prevention in the Exercised Heart: A Unique Form of Cardioprotection;548
31.7;28.7 Conclusions and Summary;549
31.8;References ;550
32;29 Antioxidative Properties of Statins in the Heart;556
32.1;29.1 Introduction;556
32.2;29.2 Properties of HMG-CoA Reductase Inhibitors (Statins);557
32.2.1;29.2.1 Mechanism Mediating Cholesterol-Dependent Effects of Statins;557
32.2.2;29.2.2 Mechanism Mediating Cholesterol-Independent Effects of Statins;558
32.3;29.3 Pathophysiology of Oxidative Stress;558
32.4;29.4 Antioxidative Effects of Statins in the Myocardium;559
32.4.1;29.4.1 Effects of Statins on Ventricular Myocardium and Cardiac Function;559
32.4.2;29.4.2 Effects of Statins on Atrial Myocardium and Atrial Fibrillation;560
32.5;29.5 Potential Effects of Statin Withdrawal;561
32.6;29.6 Summary and Conclusions;562
32.7;References;562
33;Index;566