Sauer Studies on Cardiovascular Disorders

1. Auflage 2010
ISBN: 978-1-60761-600-9
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 590 Seiten

Autoren/Hrsg.

Sauer, Heinrich

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