Marín-García Heart Failure

Bench to Bedside
1. Auflage 2010
ISBN: 978-1-60761-147-9
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 470 Seiten

Reihe: Contemporary Cardiology

Heart Failure (HF) is the final and common pathway of all cardiovascular diseases. Heart Failure: Bench to Bedside helps address a significant need to develop new paradigms and to identify novel therapeutic targets for this pervasive disease. An authoritative contribution to the field, this book provides a detailed description of new findings and emerging methodologies, as well as a critical clinical evaluation of the complex HF syndrome and future therapies. Heart Failure: Bench to Bedside includes a primer on gene profiling and bioenergetics of the normal heart and a discussion of the molecular, genetic, biochemical and cellular techniques critical to understanding HF. Further chapters discuss cardiac remodeling, oxidative stress, and alterations in other organs and systems that are often associated with HF. This book thoughtfully evaluates current and forthcoming diagnostic techniques and therapies, pharmaceutical and pharmacogenomic-based individualized medicine, gene and cell-based therapies, and the search for new frontiers. Heart Failure: Bench to Bedside presents a clear view of up-to-date approaches to clinical diagnosis and treatment, as well as offering insightful critiques of original and creative scientific thoughts on post-genomic HF research.

Autoren/Hrsg.

Marín-García, José

Inhaltsverzeichnis

1;Preface;8
2;Contents;10
3;With Contributions From;12
4;Chapter 1: Introduction to Heart Failure;15
4.1;Overview;15
4.2;Introduction;15
4.3;Prevalence and Incidence;15
4.4;Risk Factors for the Development of Heart Failure;16
4.5;Mortality and Morbidity;17
4.6;Economic Burden of Heart Failure;18
4.7;Gender, Age, and Ethnicity;18
4.8;Clinical Phenotypes of Heart Failure;21
4.8.1;Systolic vs. Diastolic Heart Failure;21
4.8.2;Acute Heart Failure Syndromes;22
4.9;Summary;23
4.10;Primer of Terminology;23
4.11;References;23
5;Chapter 2: Cardiac Function in Heart Failure: The Role of Calcium Cycling;26
5.1;Overview;26
5.2;Introduction;26
5.3;Calcium Entry Through the Plasma Membrane;26
5.4;Calcium Release from the Sarcoplasmic Reticulum;28
5.5;Calcium Sensitivity;28
5.6;Sarcoplasmic Reticulum Calcium Stores;29
5.7;Calcium Removal;29
5.8;Changes in Calcium Transients;30
5.9;Conclusions;30
5.10;Summary;30
5.11;References;30
6;Chapter 3: Gene Profiling of the Failing Heart: Epigenetics;33
6.1;Overview;33
6.2;Introduction;33
6.3;The Profiling of Gene Expression in HF;34
6.4;Global and Specific Analysis of Gene Expression;35
6.4.1;Susceptibility/Modifier Genes/RNAi in HF;35
6.5;MicroRNAs and HF;37
6.6;Epigenetics and HF;42
6.6.1;Histone/Chromatin Modifications; Epigenetic Control of Gene Expression;42
6.6.2;Histone Acetylation/Chromatin Remodeling Plays a Critical Role in the Triggering/Progression of Cardiac Hypertrophy;42
6.6.3;Other Regulators of Chromatin Remodeling Have Been Recently Identified Which May Be Operative in the Heart;43
6.7;DNA Modification-Methylation;43
6.8;Transcriptional Coactivator p300 and Cardiac Hypertrophy;45
6.9;Energy Metabolism Profiling;45
6.10;Intracellular Calcium Cycling Profiling;46
6.11;The Genetics of Human HF;47
6.12;Conclusion;48
6.13;Summary;49
6.14;References;49
7;Chapter 4: Bioenergetics and Metabolic Changes in the Failing Heart;54
7.1;Overview;54
7.2;Introduction;54
7.3;Bioenergetics of Fatty Acid and Glucose Oxidation;54
7.4;Fatty Acid and Glucose Metabolism in the Normal Cardiomyocyte;57
7.4.1;Fatty Acids Transport into the Cardiomyocyte;57
7.4.2;Glucose Transport into the Cardiomyocyte;58
7.5;Cellular Location of FAO and Glucose Oxidation;60
7.6;Secondary Effects on Mitochondrial Fatty Acid b-Oxidation: Relationship to Mitochondrial Respiration and OXPHOS;61
7.6.1;Fatty Acid Metabolism Defects Associated with Cardiomyopathy/Heart Failure;61
7.6.2;Fatty Acids and Glucose Metabolism Defects in Cardiac Remodeling and Apoptosis;62
7.7;Molecular Players and Events in Fatty Acid-Related Cardiomyopathy/HF;63
7.7.1;Genes and Modulation of Gene Expression;63
7.7.1.1;MCAD;63
7.7.1.2;VLCAD;63
7.7.1.3;CPT-II;63
7.7.1.4;MTP;63
7.7.1.5;PPAR;63
7.7.1.6;PGC-1;64
7.8;Effects of Abnormal Fatty Acid and Glucose Metabolism on Cardiac Structure/Function;64
7.9;Use of Cellular and Animal Models to Study Metabolic Defects;64
7.10;Are the Metabolic Changes Occurring in Heart Failure Tissue-Specific?;68
7.11;Diagnostics and Metabolic Therapies;69
7.11.1;Diagnostic Advances;69
7.11.2;Therapies;69
7.12;Conclusion;70
7.13;Summary;71
7.14;References;72
8;Chapter 5: The Multidimensional Role of Mitochondria in Heart Failure;80
8.1;Overview;80
8.2;Introduction;80
8.3;Centrality of Mitochondria in Cardiac Bioenergetics;80
8.4;Mitochondrial ROS Generation and Antioxidant Response;84
8.5;Mitochondrial Role in HF Apoptosis and Necrosis;86
8.6;Mitochondria in Experimental Animal Models of HF;89
8.6.1;Enzyme Dysfunction;89
8.6.2;Nuclear–Mitochondrial Communication;94
8.6.3;Mitochondrial Transcription in HF;96
8.6.4;Transgenic Mice and Mitochondria;96
8.6.5;Mitochondrial DNA Integrity and HF in Transgenic Mice;96
8.6.6;PGC-1;98
8.6.7;PPAR;99
8.6.8;Defects in Cytosolic Proteins Can Cause HF with Mitochondrial Dysfunction;100
8.6.9;Clinical Studies;101
8.7;Mitochondrial Gene Profiling;101
8.8;Implication of Metabolic Genes in HF;102
8.9;Potential Mechanisms and Downstream Effects of Metabolic Damage in HF;102
8.9.1;Calcium Handing, Homeostasis, and Contractility;103
8.10;Magnitude of Cellular and Molecular Changes Associated with Mitochondria in HF;104
8.11;What Events Occurring in HF Are Truly Tissue Specific;104
8.12;Conclusion: The Road Ahead;105
8.13;Summary;106
8.14;References;107
9;Chapter 6: Animal Models of Heart Failure;115
9.1;Overview;115
9.2;Introduction;115
9.3;Pressure and Volume Overload;115
9.4;Models of Transition of Compensated Cardiac Hypertrophy to Heart Failure;117
9.4.1;Dahl Salt-Sensitive Rats;117
9.4.2;Spontaneous Hypertensive Rats;117
9.4.3;Cardiomyopathic Hamster;118
9.5;Coronary Artery Ligation and Microembolization Models;118
9.6;Pacing Induced Cardiomyopathy;119
9.6.1;Cardiac Remodeling and Dysfunction;119
9.6.2;Fluid Retention and Edema;121
9.6.3;Neurohormonal and Cytokine Activation;121
9.7;Transgenic Models;123
9.7.1;Mutations in Sarcomeric and Intermediate Filament Proteins;123
9.7.2;Mutations and Signal Transduction Pathways;124
9.7.3;Metabolic Defects;126
9.7.4;Antioxidants and Reactive Oxygen Species;127
9.7.5;Other Genetic Animal Models;127
9.7.6;New Genetic Models;128
9.8;Conclusions;128
9.9;Summary;129
9.10;References;129
10;Chapter 7: Signaling Cascades in Heart Failure: From Cardiomyocytes Growth and Survival to Mitochondrial Signaling Pathways;135
10.1;Overview;135
10.2;Introduction;135
10.3;Signaling in Physiological Cardiovascular Growth;135
10.4;Prosurvival Pathways;136
10.4.1;Protein kinase B or Akt and PI3K;136
10.4.1.1;Akt;136
10.4.1.2;Akt in Pacing-induced HF;136
10.4.1.3;Akt, Oxidative Stress and Apoptosis;137
10.4.1.4;Akt and Mammalian Target of Rapamycin;138
10.4.1.5;Akt and Glycogen Synthase Kinase;139
10.4.1.6;Cardiac Akt Activation;139
10.4.1.7;PI3K;140
10.4.1.8;Insulin-Like Growth Factor-1: Activator of Akt Signaling;140
10.4.2;Other Growth and Pro-survival Pathways;142
10.4.2.1;SIR/Sirtuins;142
10.4.2.2;TOR;145
10.5;Signaling at the Plasma Membrane;145
10.5.1;Sarcolemmal KATP Channel;145
10.6;Signaling in the Mitochondria: Key Players;146
10.6.1;Nuclear Gene Activation;146
10.6.2;Mitochondrial Receptors;146
10.6.2.1;Reactive Oxidative Species;147
10.6.2.2;Negative Effects of ROS;147
10.6.2.3;Role of ROS in Cell Signaling;149
10.6.3;Mitochondrial KATP Channel;149
10.6.4;PT Pore;150
10.6.5;Mitochondrial Kinases;151
10.6.6;Mitochondrial Translocation;152
10.6.7;Mitochondrial Retrograde Signaling;152
10.6.8;Mitochondrial Calcium Signaling;152
10.6.9;Signals of Survival and Stress Impact Heart Mitochondria;153
10.6.9.1;Endoplasmic Reticulum;153
10.7;P53 Pathways;153
10.8;Conclusion;156
10.9;Summary;156
10.10;References;157
11;Chapter 8: Cyclic Nucleotides Signaling (Second Messengers) and Control of Myocardial Function: Effects of Heart Failure;165
11.1;Overview;165
11.2;Introduction;165
11.3;Second Messengers and Contractile Function;165
11.4;Cyclic GMP;165
11.4.1;Cyclic GMP Production: Activation of Guanylyl Cyclase;166
11.4.2;Cyclic GMP Degradation;167
11.4.3;Cyclic GMP Effectors: Cyclic GMP Protein Kinase and Cyclic GMP Affected Cyclic AMP Phosphodiesterases;167
11.4.4;Cyclic GMP Also Affects the Levels of Cyclic 167
11.5;Myocardial Hypertrophy and Failure;167
11.5.1;Alterations in Cyclic GMP and Natriuretic Peptide Levels;167
11.5.2;Cyclic GMP Has Been Implicated in Both the Process of Hypertrophy and HF;168
11.5.3;Effects of Nitric Oxide;168
11.5.4;Changes in Downstream Cyclic GMP Signaling;168
11.6;Cyclic AMP and b-Adrenergic Receptors;168
11.6.1;Cyclic AMP Effectors;169
11.6.2;Changes in Cyclic AMP Signaling in Myocardial Hypertrophy and Failure;169
11.7;a-Adrenergic Receptor Signaling;170
11.7.1;Changes in a-Adrenergic Receptor Signaling in Myocardial Hypertrophy and Failure;170
11.8;Conclusions;170
11.9;Summary;170
11.10;References;171
12;Chapter 9: Calcium Signaling: Receptors, Effectors, and Other Signaling Pathways;174
12.1;Overview;174
12.2;Introduction;174
12.3;Ca2+-Mediated Signaling;174
12.3.1;Ca2+/Sarcolemmal/Stress-Dependent Signaling Pathways;175
12.3.2;Calcineurin/Calmodulin;176
12.4;Other Kinases and Phosphatases;177
12.4.1;Protein Kinase A;177
12.4.2;Protein Kinase C;177
12.4.3;Protein Kinase G;178
12.4.4;G-Protein Regulated Kinases;179
12.4.5;MAP Kinases;179
12.5;Signaling the Receptors;180
12.5.1;Adrenergic Receptors;180
12.5.2;Muscarinic Receptors;180
12.5.3;Neurohumoral Signaling;180
12.5.3.1;Endothelin;181
12.5.3.2;Angiotensin;181
12.5.4;Growth Transcription Factors;182
12.5.5;Toll-Like Receptors;183
12.5.6;Protease Activated Receptors;184
12.5.7;Receptor Tyrosine Kinases;184
12.5.8;G-Proteins;186
12.5.9;Nuclear Receptor Transcription Factors;187
12.6;Effectors Signaling;188
12.6.1;Adenylyl Cyclase;188
12.6.2;Phospholipase C;188
12.6.3;Caveolae/Caveolins;189
12.7;Regulatory Players: Transcription Factors;189
12.7.1;NF-k.B;189
12.7.2;PPAR-a and Cofactors (RXR and PGC);190
12.8;Stress and Metabolic Signaling;190
12.8.1;Stress Signals;190
12.8.2;Metabolic Signals;190
12.9;Extracellular Signals and Matrix;191
12.10;Conclusion;191
12.11;Summary;192
12.12;References;193
13;Chapter 10: Oxidative Stress and Heart Failure;198
13.1;Overview;198
13.2;Introduction;198
13.3;ROS Production;198
13.4;Abnormal ROS Effects;199
13.5;ROS and Cell Signaling;199
13.6;ROS and Cardiac Pathology;200
13.7;Oxidative Stress, Myocardial Ischemia, and HF;202
13.8;ROS in the Aging Failing Heart;203
13.9;Oxidative Stress and Apoptosis;205
13.10;Nitric Oxide and HF;205
13.11;Antioxidant Defense;206
13.12;Antioxidants Therapy;207
13.13;Conclusion;208
13.14;Summary;209
13.15;References;210
14;Chapter 11: Cardiac Remodeling and Cell Death in Heart Failure;215
14.1;Overview;215
14.2;Introduction;215
14.3;Progression of Cardiac Remodeling and Transition to Overt HF;216
14.4;Myocardial Metabolism and Neurohormonal Signaling in Cardiac Remodeling;218
14.4.1;Insights from Transgenic Models;218
14.4.2;Neurohormonal Changes and Cytokines;219
14.4.3;Contractile Elements;220
14.4.4;Cellular Hypertrophy;220
14.4.5;Cell Death and Renewal;221
14.5;The Extracellular Matrix;223
14.5.1;Metalloproteinases;224
14.6;Electrical Remodeling Secondary to Ventricular Dysrhythmias;225
14.7;Reversing Cardiac Remodeling;226
14.7.1;Insights from Patients with Left Ventricular Assist Device;226
14.7.2;Remodeling and CRT;227
14.7.3;Other Approaches to Remodeling Therapy;227
14.8;Conclusions and Future Directions;228
14.9;Summary;229
14.10;References;230
15;Chapter 12: Heart Failure and Changes at the Periphery: Vascular, Inflammation, Neurohormonal, and Renal Systems;235
15.1;Overview;235
15.2;Introduction;235
15.3;Central and Autonomic Nervous System Perturbations;236
15.3.1;Humoral Heart–Brain Signaling;236
15.3.2;The Cytokine-CNS Connection;239
15.4;Renal Adaptation and Alterations;239
15.4.1;Abnormalities in Sensing Mechanisms;240
15.4.2;Abnormalities in Effector Mechanisms;241
15.4.3;Glomerular Hemodynamics;241
15.4.4;Physical Factors;242
15.4.5;Humoral Mechanisms;243
15.4.6;Sympathetic Nervous System;243
15.4.7;Renin–Angiotensin–Aldosterone System;243
15.4.8;Prostaglandins;245
15.4.9;Natriuretic Peptides;245
15.5;Cardiorenal Syndrome;245
15.6;Endothelial Dysfunction;247
15.7;Immune and Cytokine Activation;249
15.8;Conclusions;250
15.9;Summary;250
15.10;References;251
16;Chapter 13: Comorbidities in Heart Failure;256
16.1;Overview;256
16.2;Introduction;256
16.3;Prevalence of Comorbidities in Heart Failure;256
16.4;Diabetes Mellitus;257
16.4.1;Management of Patients with Heart Failure and Diabetes;258
16.5;Pulmonary Disorders;259
16.5.1;Obstructive Airway Disease;259
16.6;Heart Failure and Renal Dysfunction;260
16.6.1;Management of Patients with Heart Failure and Renal Dysfunction;261
16.7;Anemia and Heart Failure;262
16.8;Cognitive Dysfunction and Heart Failure in the Elderly;263
16.9;Dysrhythmias in Heart Failure;264
16.10;Atrial Fibrillation in Heart Failure;264
16.11;Conclusions;266
16.12;Summary;266
16.13;References;267
17;Chapter 14: Mechanisms and Clinical Recognition and Management of Heart Failure in Infants and Children;271
17.1;Overview;271
17.2;Introduction;271
17.3;Etiology of Heart Failure in Children;271
17.4;Growth and Nutrition;272
17.5;Clinical Signs and Symptoms;274
17.6;Fetal Heart Failure;274
17.7;Hydrops;277
17.8;Umbilical Venous Doppler;277
17.9;Heart Size;277
17.10;Treatment of Fetal Heart Failure;278
17.11;Neonatal Heart Failure;278
17.12;Developmental Changes in Cardiac Energy Metabolism;279
17.13;Right Ventricular Dysfunction in Congenital Heart Disease;280
17.14;Single Ventricle and Heart Failure;283
17.15;Pharmacology;284
17.16;Developmental Issues with Diuretics;285
17.17;Inotropic Agents in Pediatric Heart Failure;285
17.18;Phosphodiesterase Inhibitors;287
17.19;Vasodilator Therapy;287
17.20;b-Blockers;288
17.21;Conclusions;289
17.22;Summary;289
17.23;References;290
18;Chapter 15: Mechanical Circulatory Support and Heart Transplantation in Children with Severe Refractory Heart Failure;294
18.1;Overview;294
18.2;Introduction;294
18.3;Extracorporeal Membrane Oxygenation;294
18.4;Heart Transplantation in Pediatrics1;296
18.5;Recipient Age;297
18.6;Transplant Indications: Complex Anatomy;298
18.7;Transplant Indications: Hypoplastic Left Heart Syndrome;298
18.8;Unique Expansion of Donor Pool;298
18.9;Surveillance for Rejection;299
18.9.1;Definitions;299
18.9.2;Acute Rejection;299
18.9.3;Echocardiographic Rejection Surveillance in Infant Recipients;299
18.10;EMB-Based Surveillance Strategies;300
18.11;Noninvasive Surveillance of Acute Rejection;301
18.12;Late Outcomes Following Pediatric Heart Transplantation;301
18.13;Late Rejection and Graft Atherosclerosis;301
18.14;Late Outcomes: Quality of Life Following Pediatric Heart Transplantation;303
18.15;Unique Pediatric Donor and Recipient Immunologic Variables;303
18.16;Immunosuppression in Pediatric Heart Transplant Recipients;304
18.17;Infection/Malignancies in Pediatric Heart Transplant Recipients;305
18.18;Conclusions;306
18.19;Summary;306
18.20;References;306
19;Chapter 16: Basic Mechanisms Mediating Cardiomyopathy and Heart Failure in Aging;311
19.1;Overview;311
19.2;Introduction;311
19.3;Accumulation of Reactive Oxygen Species;311
19.4;Inflammatory Mechanisms/Signaling;314
19.4.1;Adrenergic Receptors in the Aging Heart;314
19.4.2;Cardiac G-Protein-Coupled Receptors;315
19.4.3;SERCA and Thyroid Hormone in the Aging Heart;316
19.4.4;Growth Hormone and IGF-I;317
19.4.5;Cellular Damage/Cell Loss;318
19.5;Telomeres and Telomere-Related Proteins;318
19.6;Autophagy and Cardiac Aging;320
19.7;Myocardial Remodeling and Aging;321
19.8;Hypertrophic Cardiomyopathy;324
19.9;Dilated Cardiomyopathy;325
19.10;Restrictive Cardiomyopathy;329
19.11;Conclusion;330
19.12;Summary;330
19.13;References;331
20;Chapter 17: Heart Failure of Aging: Clinical Considerations;337
20.1;Overview;337
20.2;Introduction;337
20.3;Pathophysiologic Considerations;337
20.4;Clinical Considerations;338
20.4.1;Etiologies and Precipitating Factors;338
20.4.2;Clinical Presentation and Diagnostic Challenges;338
20.4.3;Biomarkers in the Diagnosis of Heart Failure in the Elderly;339
20.4.4;Pharmacological Therapy;340
20.4.5;Disease Management Programs for Heart Failure in the Elderly;341
20.4.6;Device and Cardiac Replacement Therapy in the Elderly;341
20.5;Conclusions and Future Directions;343
20.6;Summary;343
20.7;References;344
21;Chapter 18: Diagnosis of Heart Failure: Evidence-Based Perspective;347
21.1;Overview;347
21.2;Introduction;347
21.3;General Considerations Relevant to the Diagnosis of Heart Failure;348
21.4;Clinical Evaluation of Patients with Heart Failure;349
21.5;Role of Echocardiography in the Diagnosis of Heart Failure;351
21.5.1;Heart Failure with Systolic Dysfunction;351
21.5.2;Valvular Regurgitation;352
21.5.3;Heart Failure with Preserved Systolic Function;352
21.6;Other Diagnostic Tests;353
21.7;Biomarkers in the Diagnosis of Heart Failure;353
21.8;Conclusions;354
21.9;Summary;355
21.10;References;355
22;Chapter 19: “Omics” Application in Heart Failure: Novel Diagnostic and Prognostic Markers to Understand Pathophysiology and Find New Therapies;358
22.1;Overview;358
22.2;Introduction;358
22.3;Use of Gene Profiling and Proteomics in HF;358
22.4;Proteome Analysis in HF;360
22.5;Metabolome in HF;361
22.6;Metabolic Imaging;362
22.7;Assessment of Genetic Influences on Drug Targets and Drug Metabolism in HF;363
22.8;Pharmacogenetics/Pharmacogenomics;363
22.9;Use of Cardiac Expression Modules/Integrative Bioinformatics in HF;364
22.10;Systems Biology: An Integrated Approach to HF;365
22.11;Conclusions and Future Directions;366
22.12;Summary;367
22.13;References;368
23;Chapter 20: Treatment of Chronic Heart Failure;371
23.1;Overview;371
23.2;Introduction;371
23.3;General Measures;371
23.4;Pharmacologic Therapy;373
23.5;Cardiac Resynchronization Therapy;374
23.6;Internal Cardiovertor Defibrillator Therapy;377
23.7;Heart Transplantation;379
23.8;Conclusions;380
23.9;Summary;381
23.10;References;382
24;Chapter 21: Gene Therapy in Heart Failure: Forthcoming Therapies;385
24.1;Overview;385
24.2;Introduction;385
24.3;Why Gene Therapy for Cardiovascular Disease?;385
24.3.1;Vectors and Targets;385
24.3.2;Nature of Targeted Gene;386
24.4;Specific Examples of Cardiovascular Gene Therapy-Preclinical Studies;387
24.4.1;Coronary Artery Restenosis;387
24.4.2;Therapeutic Angiogenesis (Increasing Proliferation of Blood Vessels) to Limit Ischemia;388
24.4.3;Hypertension;388
24.4.4;Cardiac Dysrhythmias;390
24.4.5;Myocarditis;390
24.4.6;Myocardial Protection;390
24.4.7;Heart Failure;390
24.5;Clinical Studies of Cardiovascular Gene Therapy Thus Far;391
24.5.1;Gene-Targeting Approaches;392
24.5.2;Ribozymes;392
24.5.3;Antisense Oligonucleotides;392
24.5.4;RNA Interference;394
24.6;Conclusions and Future Directions;396
24.7;Summary;396
24.8;References;398
25;Chapter 22: Myocardial Cell-Based Regeneration in Heart Failure;401
25.1;Overview;401
25.2;Introduction;401
25.3;Stem Cell Therapy;401
25.4;Advantages of ES Cell Transplantation;403
25.5;Limitations and Concerns with ESC Transplantation;404
25.5.1;Recommendations;405
25.6;Adult Skeletal Myoblast Cells;405
25.6.1;Advantages to Myoblast Transplantation;405
25.6.2;Limitations and Concerns with Myoblast Transplantation;406
25.6.3;Further Recommendations;406
25.6.4;Trials with Autologous Skeletal Myoblast Transfer;406
25.7;Adult Bone Marrow Derived Stem Cells;407
25.7.1;Advantages of Adult BM Cells Transplantation;407
25.7.2;Limitations/Concerns with Adult BMC Transplant;407
25.7.2.1;How Does the Preceding Information Translate to Human Clinical Studies?;408
25.8;Cardiac Stem Cells;408
25.8.1;Adult Cardiac Stem Cells from Human and Animal Models;408
25.8.2;Advantages of ACS Cells;409
25.8.3;Limitations of ACS Cells;409
25.8.4;Recommendations;410
25.9;Human Cardiac Stem Cells;410
25.10;Finding Cell Identity;411
25.11;Which Stem Cell Type to Use for HF;411
25.12;Other Developing Technologies in Cell Engineering;411
25.13;Conclusions and Future Directions;413
25.14;Summary;414
25.15;References;416
26;Chapter 23: Future Frontiers in Heart Failure;421
26.1;Overview;421
26.2;Introduction;421
26.3;Present and Emerging Concepts in the Integrative Approach to HF;421
26.3.1;Cardiac Biomarkers;422
26.3.2;Proteomics in the Discovery of New Markers;423
26.3.3;Microarray and Genetic Biomarkers;424
26.4;Role of Mitochondria;424
26.5;Bionics Role in HF;425
26.6;Modeling Systems Approaches;426
26.7;Translation of Findings from the Bench into Clinical Application;427
26.8;Diagnostic Challenges and Genetic Counseling;428
26.9;New and Future Therapeutic Options in Cardiovascular Medicine; Postgenomic Contributions;429
26.10;Bioengineering;429
26.11;Vessel Engineering;430
26.12;Genetic Engineering;431
26.13;Bioinformatics/Computational Biology in HF;431
26.14;Conclusion;431
26.15;Summary;432
26.16;References;433
27;Glossary;437
28;Index;449