Essentials of Restenosis (eBook)

PREFACE 6
CONTENTS 7
CONTRIBUTORS 9
I PATHOPHYSIOLOGY AND DIAGNOSIS 30
Unraveling the Complex Process of Restenosis From Bench to Bedside 31
INTRODUCTION 31
Epidemiology and Pathogenesis of Restenosis 34
SCOPE AND EPIDEMIOLOGY OF RESTENOSIS 34
PATHOGENESIS OF RESTENOSIS 37
DISCUSSION 49
REFERENCES 49
Clinical Presentation of Restenosis 56
INTRODUCTION 56
TIMING OF RESTENOSIS 57
SILENT ISCHEMIA 58
CHEST PAIN 63
MI AND DEATH 67
CONCLUSIONS 68
REFERENCES 69
Pathological Anatomy of Restenosis 74
INTRODUCTION 74
BARE METAL STENTS AND VASCULAR HEALING IN ANIMAL MODELS 75
HEALING IN HUMAN STENTED CORONARY ARTERIES 75
SMC PROLIFERATION 77
THE EXTRACELLULAR MATRIX 77
DIFFERENCE IN ARTERIAL HEALING BETWEEN HUMANS AND ANIMALS 78
INFLAMMATION AND RESTENOSIS: THE RELATIONSHIP TO VESSEL INJURY AND PLAQUE TYPE 80
ANGIOGENESIS AND NEOINTIMAL FORMATION AND INFLAMMATION 81
PLAQUE CHARACTERISTICS AND RESTENOSIS 82
THE INFLUENCE OF DIABETES ON RESTENOSIS 82
DES AND HEALING IN PRECLINICAL STUDIES 83
REFERENCES 83
The Influence of Shear Stress on Restenosis 86
SHEAR STRESS AND VASCULAR (PATHO) BIOLOGY 86
SHEAR STRESS IN PATIENTS 89
SHEAR STRESS AND RESTENOSIS AFTER BALLOON ANGIOPLASTY 91
SHEAR STRESS AND RESTENOSIS AFTER STENTING 94
CONCLUSIONS 105
REFERENCES 105
The Immune System in the Pathogenesis of Vascular Proliferative Disease 111
INTRODUCTION: THE INTERVENTIONAL CARDIOLOGIST AND MODERN IMMUNOLOGY 112
ATHEROSCLEROSIS AS AN INFLAMMATORY DISEASE 112
IS THE IMMUNE SYSTEM INVOLVED IN VASCULAR DISEASE? 114
SELECTED IMMUNE SYSTEM BASICS 115
PREVAILING DOGMA: ACTIVATION OF PRIMARY LYMPHOCYTES IN THE LYMPH NODE 132
PLAQUE TYPE AND VASCULAR-ASSOCIATED LYMPHOID TISSUE 134
EVIDENCE FROM ANIMAL MODELS FOR IMMUNE SYSTEM INVOLVEMENT 135
ROLE OF NONPATHOGENIC MICROBES AND INFECTIONS 135
MECHANISMS BY WHICH MICROBES AND INFECTION MAY AFFECT ATHEROSCLEROSIS 141
RECIPROCAL INTERACTIONS BETWEEN INFLAMMATION AND LIPID METABOLISM 143
OPTIONS FOR INTERVENTION AND RESEARCH 147
ACKNOWLEDGMENTS 148
KEY POINTS ON IMMUNITY AND LIPIDS 148
KEY POINTS ON PLAQUE ASPECTS 148
KEY POINTS ON MAIN CELLULAR PLAYERS AND ANTIGENS INVOLVED IN ATHEROGENESIS 148
ABBREVIATIONS 149
REFERENCES 150
Animal Restenosis Models 157
INTRODUCTION 157
ANIMAL RESTENOSIS MODELS IN COMMON USE 157
IS THERE A SPECIES-SPECIFIC ARTERIAL RESPONSE TO ARTERIAL INJURY? 161
DRUG STUDIES 165
CONCLUSIONS: THE IDEAL STUDY 170
REFERENCES 171
II GENETIC BASIS OF RESTENOSIS 177
The Genomics of Restenosis 178
INTRODUCTION 178
AN INTRODUCTION TO GENOMICS 179
GENOMIC TOOLS 180
APPLICATION OF GENOMICS TO RESTENOSIS 185
EXISTING DATA WITHIN THE FIELD OF RESTENOSIS GENOMICS 186
FUTURE DIRECTIONS 187
SUMMARY 187
GLOSSARY 188
REFERENCES 189
Gene-Expression Profiling and Restenosis 191
INTRODUCTION 191
TECHNICAL APPROACH TO GENE-EXPRESSION PROFILING 192
PCR-BASED APPROACHES 192
ELUCIDATION OF MECHANISMS OF RESTENOSIS 193
IN VITRO EXPERIMENTS 194
ANIMAL EXPERIMENTS 194
STUDIES IN PATIENTS 194
THERAPEUTIC DEVELOPMENT 195
PERSPECTIVES 196
REFERENCES 196
Proteomics and Restenosis 198
INTRODUCTION 198
PROTEOMICS 199
METHODS 200
PROTEOMICS IN RESTENOSIS 204
SUMMARY 204
REFERENCES 205
Contribution of Circulating Progenitor Cells to Vascular Repair and Lesion Formation 207
INTRODUCTION 207
CONTRIBUTION OF SMCS TO VASCULAR LESIONS 207
CONTRIBUTION OF BONE MARROW CELLS TO VASCULAR LESIONS 209
THERAPEUTIC STRATEGIES TARGETING CIRCULATING VASCULAR PROGENITOR CELLS 214
CONCLUSIONS 216
REFERENCES 216
Cell Cycle Regulators and Vascular Proliferative Diseases 220
INTRODUCTION 220
ATHEROSCLEROSIS 221
VSMC HYPERPLASIA 221
STEM CELLS 222
CELL CYCLE 224
CELL CYCLE REGULATION AND VSMC HYPERPLASIA 228
MOLECULAR TARGETS FOR VASCULAR THERAPIES 229
REFERENCES 229
Arterial Remodeling 234
INTRODUCTION 234
ARTERIAL REMODELING AFTER ANGIOPLASTY 234
ARTERIAL REMODELING AND ECM TURNOVER 236
ARTERIAL REMODELING AND PROTEASE ACTIVITY 237
ARTERIAL REMODELING: A ROLE FOR IMMUNITY? 238
ARTERIAL REMODELING: INTERVENTIONS 239
ARTERIAL REMODELING: CONCLUSIONS 241
REFERENCES 241
The Role of eNOS in Vascular Diseases 247
THREE ISOFORMS OF NOS 247
SYNTHESIS OF NO 248
REGULATION OF NO PRODUCTION 248
MEASUREMENT OF NO PRODUCTION 250
MECHANISMS OF DECREASED NO BIOAVAILABILITY 250
ROLE OF NO IN PATHOGENESIS OF VASCULAR DISEASES 252
KEY NOTES 259
REFERENCES 259
III DIAGNOSIS OF RESTENOSIS 264
The Use of Pressure Gradient in the Diagnosis of Restenosis 265
INTRODUCTION 265
DEFINITION OF FRACTIONAL FLOW RESERVE 266
CLINICAL VALIDATION OF FRACTIONAL FLOW RESERVE 267
PRACTICAL SET-UP OF PRESSURE MEASUREMENTS IN THE CATHETERIZATION LABORATORY 268
APPLICATION OF PRESSURE MEASUREMENTS IN THE DIAGNOSIS OF RESTENOSIS 269
COST-EFFECTIVENESS OF FRACTIONAL FLOW RESERVE 269
LIMITATIONS 270
CONCLUSIONS 272
REFERENCES 273
The Use of Radio Isotopes in the Diagnosis of Vascular Proliferative Disease 275
INTRODUCTION 275
MPI WITH RADIONUCLIDES 276
IMAGING THE VASCULAR PROLIFERATIVE DISEASE PROCESS 278
MPI IN PATIENTS AFTER PCI 280
SUMMARY STATEMENTS 290
CONCLUSIONS 290
REFERENCES 291
Magnetic Resonance Imaging for Restenosis 294
INTRODUCTION 294
SAFETY OF STENTS 294
STENT RELATED ARTEFACTS 295
MR FLOW MEASUREMENTS 296
MR COMPATIBLE (TRANSPARENT) STENTS 296
SUMMARY 300
REFERENCES 300
Coronary Imaging With Multislice Spiral Computed Tomography 303
INTRODUCTION 303
CARDIAC CT 304
DETECTION OF CORONARY STENOSIS 308
PLAQUE IMAGING 309
IMAGING OF CORONARY ARTERIES WITH STENTS 309
CONCLUSION 312
REFERENCES 312
IV THERAPY OF RESTENOSIS 314
Pharmacotherapy of Restenosis 315
INTRODUCTION 315
PHARMACOTHERAPY FOR RESTENOSIS AFTER BALLOON ANGIOPLASTY: THE EARLIER STUDIES 315
PHARMACOTHERAPY FOR RESTENOSIS AFTER BALLOON ANGIOPLASTY: THE LATER STUDIES 316
PHARMACOLOGICAL TREATMENT TO PREVENT IN- STENT RESTENOSIS 317
PHARMACOLOGICAL TREATMENT FOR PREVENTION OF MAJOR ADVERSE EVENTS AFTER STENT- IMPLANTATION 317
REFERENCES 319
Brachytherapy 321
INTRODUCTION 321
THE CLINICAL TRIALS 322
TRIALS OF 323
RADIATION 323
WRIST SERIES 327
TRIALS 330
CLINICAL TRIALS OF 331
RADIATION 331
CLINICAL TRIALS WITH RADIOACTIVE EMITTING STENTS 341
CONTROVERSIES IN VASCULAR BRACHYTHERAPY 342
KEY POINTS/CONCLUSIONS 343
REFERENCES 343
Preclinical Data of Eluting Stents 347
INTRODUCTION 347
RESTENOSIS AFTER ANGIOPLASTY AND AFTER STENTING: TWO DIFFERENT MECHANISMS 348
PATHOPHYSIOLOGY OF IN-STENT RESTENOSIS 349
ANIMAL MODELS 351
COMPARISON OF VASCULAR HEALING IN ANIMALS AND HUMANS 352
DRUG-ELUTING STENTS 352
DES BIOCOMPATIBLE MATERIALS 354
DES WITH PROHEALING AGENTS 354
DES WITH CORTICOSTEROIDS 355
DES WITH ANTIMITOTIC AGENTS 355
REFERENCES 362
Clinical Data of Eluting Stents 367
INTRODUCTION 367
STENTS ELUTING ANTI-INFLAMMATORY AGENTS 368
STENTS ELUTING IMMUNOSUPPRESSIVE AGENTS 368
SIROLIMUS-ELUTING STENTS 368
SIROLIMUS ANALOGS ELUTING STENTS 373
TACROLIMUS-ELUTING STENTS 373
MYCOPHENOLIC ACID-ELUTING STENT 373
STENTS ELUTING ANTIPROLIFERATIVE AGENTS 374
PACLITAXEL-ELUTING STENTS 374
POLYMER-BASED TAXOL-ELUTING STENTS 374
NONPOLYMER-BASED TAXOL-ELUTING STENTS 375
ACTINOMYCIN-ELUTING STENTS 376
ANGIOPEPTIN-ELUTING STENTS 376
STENT-ELUTING EXTRACELLULAR MATRIX MODULATORS 376
PROHEALING ELUTING STENTS 376
NITRIC OXIDE-ELUTING STENTS 377
ESTRADIOL-ELUTING STENTS 377
REAL WORLD CLINICAL DATA 377
STENT DEPLOYMENT TECHNIQUE 378
FUTURE DES INDICATIONS 379
REFERENCES 380
Biodegradable Stents 382
THE ROLE OF STENTS IN PERCUTANEOUS CORONARY INTERVENTION 382
HISTORY OF THE BIODEGRADABLE STENT 383
HISTORY OF THE IGAKI–TAMAI STENT 383
APPLICATION OF THE IGAKI–TAMAI STENT TO HUMAN CORONARY ARTERIES 384
TIME-COURSE OF IVUS FINDINGS AFTER IMPLANTATION OF THE IGAKI – TAMAI STENT 387
CONCLUSIONS 388
REFERENCES 388
V BIOTECHNOLOGY IN THE TREATMENT OF RESTENOSIS 389
Vascular Gene Therapy 390
INTRODUCTION 390
VASCULAR GENE-TRANSFER VECTORS 392
NONVIRAL VECTORS 393
VIRAL VECTORS 394
PROMOTERS FOR VASCULAR GENE TRANSFER 396
THE INTERFACE OF VECTORS, PROMOTERS, AND THE FUTURE 401
REFERENCES 403
Antisense and ODN Transcription Factors in the Treatment of Vascular Proliferative Disease 406
INTRODUCTION 406
GENE THERAPY OF INTIMAL HYPERPLASIA 407
RATIONALE FOR USING ANTISENSE OLIGONUCLEOTIDES IN THE TREATMENT OF INTIMAL HYPERPLASIA 408
EFFICACY OF ANTISENSE OLIGONUCLEOTIDES IN THE INHIBITION OF SMC PROLIFERATION AND THE PREVENTION OF RESTENOSIS 409
DELIVERY SYSTEMS FOR ANTISENSE OLIGONUCLEOTIDES 410
CLINICAL IMPLICATIONS AND FIRST EXPERIENCE OF ANTISENSE THERAPY IN THE TREATMENT OF VASCULAR PROLIFERATIVE DISEASE 411
CONCLUSION 414
ACKNOWLEDGMENTS 414
REFERENCES 414
Cell Cycle Approaches to the Treatment of In- Stent Restenosis 418
INTRODUCTION 418
THE CELL CYCLE: CYCLINS, CDKS, AND CDK INHIBITORS 419
p27Kip1 AND p21Cip1 FUNCTION 420
THE CDKS AND CKIS IN VASCULAR REMODELING 421
CLINICAL APPLICATION OF THE CKIS 422
REFERENCES 426
Local Gene and Cell Delivery Devices 429
INTRODUCTION 429
LOCAL DELIVERY DEVICES 432
DOUBLE BALLOON CATHETER 433
DISPTACH 434
CATHETER 434
POROUS AND MICROPOROUS BALLOONS 435
CHANNELED BALLOON CATHETER 438
INFUSASLEEVE CATHETER 438
HYDRO-GEL ANGIOPLASTY BALLOON 439
INFILTRATOR CATHETER 441
IONTOPHORETIC BALLOON 443
STENTS 444
COMPARISONS OF LOCAL DELIVERY DEVICES 445
CONCLUSION 448
REFERENCES 448
INDEX 453