Vascular Protection: Molecular Mechanisms, Novel Therapeutic Principles and Clinical Applications (Endothelial Cell Research)

Book Cover......Page 1
Half-Title......Page 2
Title......Page 4
Copyright......Page 5
Contents......Page 6
Preface......Page 11
List of Contributors......Page 12
INTRODUCTION......Page 17
PHYSIOLOGICAL ROLE OF ENDOTHELIAL NO......Page 18
REGULATION OF ENDOTHELIAL NO AVALIABILITY......Page 19
NOS-III mRNA stability......Page 20
Posttranslational modification, cellular localization and protein-protein interactions......Page 21
Endogenous inhibitor......Page 22
Atherosclerosis......Page 23
Peripheral Arterial Occlusive Disease......Page 25
Hypertension......Page 26
Cardiovascular Complications of Diabetes......Page 27
THERAPEUTIC RESTORATION OF ENDOTHELIAL NO PRODUCTION AND ITS CONTRIBUTION TO TREATMENT BENEFITS IN CARDIOVASCULAR DISEASES......Page 28
Effect of E2 in L-NAME Treated Rabbits......Page 29
Effect of Simvastatin on Stroke in NOS-III-KO Mice......Page 30
ACE-Inhibitors......Page 31
Antioxidant Vitamins......Page 32
L-Arginine......Page 33
Gene Therapy......Page 34
CONCLUSION......Page 35
REFERENCES......Page 36
INTRODUCTION......Page 46
Sickle RBC Interaction with Endothelial Cells......Page 47
Adhesion of SS RBC Induce Oxidant Stress in Endothelial Cells......Page 48
SS RBC Induce the Expression of Cell Adhesion Molecules in HUVEC......Page 49
SS RBC Increase the Migration of Monocytes......Page 50
Conclusions......Page 51
Acknowledgements......Page 53
REFERENCES......Page 54
ATHEROSCLEROSIS AND ENDOTHELIAL DYSFUNCTION......Page 57
NOS UNCOUPLING: eNOS AS A BIPOLAR MOLECULAR SWITCH.......Page 59
Heme: The Molecular Assembly Line......Page 61
Quantification of NO—Superoxide Balance......Page 62
CONCLUSION......Page 63
REFERENCES......Page 64
4. Endothelin Receptor Changes Following Angioplasty of Porcine Coronary Arteries: Effect of the Endothelin-A Receptor Antagonist, LU 135252......Page 69
Endothelin-1......Page 70
In Vitro Autoradiography......Page 71
DISCUSSION......Page 72
REFERENCES......Page 75
5. A Potential Role for Endothelin-1 in Peripheral Vascular Disease......Page 79
Tissue Collection, Storage and Preparation......Page 80
Calf Muscle Biopsies......Page 81
Endothelin-1-Like Immunoreactivity (ET-1-LI)......Page 82
ET-1-Induced Vasoconstriction......Page 83
Mitogenic Actions of ET-1......Page 85
Role of Microvessels in Ischaemia and PVD......Page 86
REFERENCES......Page 87
INTRODUCTION......Page 89
Study Population......Page 90
Results......Page 91
Discussion......Page 94
Purpose......Page 95
Discussion......Page 96
REFERENCES......Page 97
7. Effect of AT1-Receptor Antagonists on Endothelial Function......Page 100
ACE-inhibitors......Page 101
AT1 Receptor Antagonists......Page 102
Animal Experiments......Page 103
Clinical Tests......Page 104
FMD Testing of Healthy Individuals......Page 105
Tests on Patients with Hypertension......Page 106
CONCLUSION......Page 107
REFERENCES......Page 108
INTRODUCTION......Page 111
Vein Harvesting Technique......Page 112
Important Notes......Page 113
Endothelial Integrity......Page 114
Angiographic Follow-Up......Page 115
DISCUSSION......Page 117
REFERENCES......Page 119
INTRODUCTION......Page 121
NO Production in Media and Adventitia......Page 122
Soluble Guanylyl Cyclase and the cGMP Pathway......Page 124
Superoxide Ions and Formation of Peroxynitrite......Page 125
Nitrosation of Thiols......Page 126
Formation of Dinitrosyl Iron Complexes with Thiols......Page 127
REFERENCES......Page 129
eNOS......Page 134
Ca2+-DEPENDENT eNOS ACTIVATION......Page 135
MECHANICAL STIMULI AND Ca2+ -INDEPENDENT NO PRODUCTION......Page 136
Shear Stress and NO Production......Page 137
NO Production Elicited by Isometric Contraction......Page 138
PHOSPHORYLATION......Page 140
REFERENCES......Page 144
INTRODUCTION......Page 147
CD11b CD18 on Monocytes......Page 148
RECEPTOR FOR AGE (RAGE)......Page 149
RAGE INDUCTION OF OXIDANT STRESS......Page 150
CONCLUSION......Page 151
REFERENCES......Page 152
INTRODUCTION......Page 153
NF-κB/IκB Family Members......Page 154
IκB Kinase......Page 155
Direct Phosphorylation of NF-κB......Page 156
Atherosclerosis......Page 157
Septic shock......Page 158
NF-κB/IκB Protein Subunits Present in Human Vascular Smooth Muscle......Page 159
Oxidant stress......Page 160
cAMP......Page 161
Nitric oxide......Page 162
CONCLUSION......Page 163
REFERENCES......Page 164
INTRODUCTION......Page 169
Activation of ERK1/2 by Flow......Page 171
Activation of JNK by Flow......Page 172
CONCLUSIONS......Page 173
REFERENCES......Page 175
THE “SOIL” FOR ATHEROSCLEROSIS......Page 177
ORIGINS OF THE INTIMA......Page 179
MECHANISMS OF NATURAL INTIMAL FORMATION......Page 180
UNIQUE PROPERTIES OF INTIMAL CELLS......Page 181
DOES CLONALITY EXPLAIN THE PROLIFERATION PARADOX?......Page 182
ANALYSIS OF PLAQUE RUPTURE USING ANIMAL MODELS OR HUMAN TISSUE......Page 183
ROLE OF THE PLAQUE SMOOTH MUSCLE CELL IN PLAQUE RUPTURE......Page 186
INTIMAL MASS DOES NOT EXPLAIN LOSS OF LUMEN......Page 187
ROLE OF INTIMAL WOUND HEALING IN LOSS OF LUMEN......Page 189
REFERENCES......Page 190
15. Macrophage Resistance to Apoptosis in Vascular Diseases......Page 196
MACROPHAGE INTERACTION WITH NITRIC OXIDE (NO)......Page 197
APOPTOSIS......Page 198
MACROPHAGE APOPTOSIS AND CELL CYCLE REGULATION......Page 200
CASPASE ACTIVITY......Page 201
REFERENCES......Page 202
INTRODUCTION......Page 206
Cytokines Favoring Apoptosis......Page 207
Cytokines Favoring Survival and Proliferation.......Page 210
SIGNALING PATHWAYS THROUGH WHICH INFLAMMATION, SURVIVAL AND APOPTOSIS ARE REGULATED......Page 211
Pathways Contributing to Apoptosis......Page 212
Pathways That Contribute to Survival......Page 213
Pathways that can Contribute to Both Survival and Apoptosis......Page 215
CONCLUDING REMARKS......Page 217
REFERENCES......Page 218
INTRODUCTION......Page 221
VSMC Polyploidization at Capacitance Arteries of Hypertensive Rats......Page 222
Altered Mitotic Spindle Cell Cycle Checkpoint in VSMC of Prehypertensive Rats......Page 224
CONCLUSIONS......Page 227
REFERENCES......Page 228
INTRODUCTION......Page 230
EPIDEMIOLOGY AND AETIOLOGY OF VEIN GRAFT FAILURE......Page 231
INNERVATION OF VEINS, ARTERIES AND VEIN GRAFTS......Page 232
NEURAL REORGANISATION IN PORCINE VEIN GRAFTS......Page 234
ENDOTHELIN DISTRIBUTION......Page 238
INNERVATION AND VEIN GRAFT PATHOLOGY......Page 239
CONCLUDING REMARKS......Page 240
REFERENCES......Page 241
INTRODUCTION......Page 244
REPRODUCTIVE PHENOTYPES OF ER KNOCKOUT MODELS......Page 245
OVARY AND OVARIAN HORMONES......Page 246
MAMMARY GLAND......Page 248
NON-REPRODUCTIVE TISSUES......Page 249
PROGESTERONE ACTION IN THE αERKO FEMALE......Page 250
SUMMARY......Page 251
REFERENCES......Page 252
INTRODUCTION......Page 254
AORTA OF MALE MICE HAS A HIGHER NUMBER OF ESTRADIOL BINDING SITES, HIGHER ENDOTHELIAL NITRIC OXIDE PRODUCTION AND IS MORE RESISTANT TO DIET INDUCED ATHEROSCLEROSIS THAN AORTA OF FEMALE MICE......Page 255
Decreased EDNO Production in ERKO Mouse Aorta......Page 256
ENDOTHELIAL DYSFUNCTION AND PREMATURE CORONARY ARTERIOSCLEROSIS IN A MALE PATIENT WITH GENETIC MUTATION IN THE ERα GENE......Page 258
ER DEFICIENCY LEADS TO INCREASE IN CARDIAC L-TYPE CA2+ CHANNELS IN ERKO MICE: EVIDENCE FOR A CARDIOPROTECTIVE ROLE OF ER......Page 260
SUMMARY AND CONCLUSIONS......Page 262
ACKNOWLEDGEMENTS......Page 264
REFERENCES......Page 265
INTRODUCTION......Page 269
Animals......Page 270
Animals......Page 271
RESULTS......Page 272
Apo E-/- Mouse Studies......Page 273
DISCUSSION......Page 274
REFERENCES......Page 275
INTRODUCTION......Page 280
MATERIALS AND METHODS......Page 281
RESULTS......Page 282
DISCUSSION......Page 283
CONCLUSION......Page 285
REFERENCES......Page 286
INTRODUCTION......Page 288
Study Population......Page 290
Measurement of Lp(a) Lipoprotein and TGF- 1......Page 291
Levels of Lp(a) Lipoprotein......Page 292
DISCUSSION......Page 294
REFERENCES......Page 296
THE RENIN ANGIOTENSIN SYSTEM......Page 299
Angiotensin II in Cardiovascular Disease......Page 300
History......Page 301
Human Heart Chymase......Page 303
Chymase in Human Vascular Tissues......Page 304
Chymase Localisation......Page 305
Species Differences......Page 307
ACE Inhibitors......Page 308
Receptor Antagonists......Page 309
CONCLUSION......Page 310
REFERENCES......Page 311
Insulin Secretion and Action......Page 316
Pre-Receptor Causes......Page 317
Insulin Resistance and Syndrome X......Page 318
Secretion and Processing of PAI-1......Page 319
PAI-1 and Atherogenesis......Page 320
Insulin Action, Insulin Resistance and PAI-1......Page 321
SUBJECTS AND METHODS......Page 322
RESULTS......Page 323
DISCUSSION......Page 324
REFERENCES......Page 325
26. Antiatherothrombotic Actions of Statins are Mediated by the Arterial Wall......Page 333
Statistical Methods......Page 334
RESULTS......Page 335
DISCUSSION......Page 337
REFERENCES......Page 338
INTRODUCTION......Page 340
Pathophysiologic Aspects......Page 341
Therapeutical and Pharmacological Aspects......Page 342
Pathophysiological Aspects......Page 343
Clinical Aspects......Page 344
REFERENCES......Page 345
THE FIBRINOLYTIC SYSTEM......Page 348
PAI-1......Page 349
Transforming Growth Factor Beta (TGF-β)......Page 352
Tissue Factor......Page 353
Central Role of TNF- in the Obese Phenotype......Page 354
Central Role of the Adipocyte in the Obese Phenotype......Page 355
REFERENCES......Page 356
29. Characterization of Platelets in Patients with Inherited Large Platelet Syndrome......Page 358
Prothrombotic effects of platelets......Page 359
Inflammatory Products......Page 360
Primary or Secondary Large Platelet Syndrome: Mechanisms for the Development of Large Platelets......Page 361
Test Subjects......Page 362
P-Selectin in Relation to Large Platelets......Page 363
CHARACTERIZATION OF PLATELET PROTEINS IN NORMAL AND LARGE SIZED PLATELETS BY 2D GEL ANALYSIS......Page 364
REFERENCES......Page 365
OVERVIEW OF STUDIES COMPARING PERIPHERAL AND INTRACARDIAC INDICES OF HYPERCOAGULABILITY......Page 368
DISCUSSION......Page 370
ACKNOWLEDGEMENTS......Page 371
REFERENCES......Page 372
31. Gene Therapy for Cardiovascular Diseases: An Overview......Page 373
I. CARDIOVASCULAR GENE THERAPY STRATEGIES......Page 374
II. CARDIOVASCULAR GENE THERAPY DELIVERY SYSTEMS......Page 375
Adenoviral Vectors......Page 378
Fusigenic-Liposome Mediated Gene Transfer (HVJ-Liposomes)......Page 379
III. GENE THERAPY IN THE HEART......Page 380
A. Gene Therapy for Neovascularization......Page 381
B. Gene Therapy to Enhance Contractility......Page 384
C. Gene Therapy for Myocardial Infarction......Page 385
A. Gene and Oligonucleotide Therapy of Restenosis......Page 386
B. Gene and Oligonucleotide Therapy of Vein Graft Failure......Page 389
V. GENE THERAPY FOR HYPERLIPIDEMIA AND SYSTEMIC DISEASES......Page 391
B. In Vivo Approach......Page 392
VII. REFERENCES......Page 393
INTRODUCTION......Page 398
ANGIOGENESIS: A RESPONSE TO ISCHEMIA......Page 399
ANGIOGENESIS AND NITRIC OXIDE......Page 400
ADMA: AN ENDOGENOUS INHIBITOR OF NO SYNTHESIS......Page 401
IS ADMA AN ENDOGENOUS ANTI-ANGIOGENIC AGENT?......Page 403
REFERENCES......Page 406
INTRODUCTION......Page 409
L-arginine......Page 410
Phytoestrogens......Page 411
Pharmacokinetics of the Nutrient Bar......Page 412
The Nutrient Bar and Endothelial Function in Hypercholesterolemia & CAD......Page 414
The Nutrient Bar and Endothelial Function in Peripheral Arterial Disease......Page 415
Subjects......Page 416
Outcomes measures......Page 417
Evaluation of efficacy......Page 419
Biochemical studies......Page 420
Adverse events from pharmacokinetic study......Page 421
DISCUSSION......Page 422
REFERENCES......Page 423
INTRODUCTION......Page 427
THE ENDOTHELIUM......Page 428
VASCULAR SMOOTH MUSCLE CELLS......Page 429
CELLULAR INTERACTIONS AND PLAQUE STABILITY......Page 430
IMPLICATIONS FOR CLINICAL EVALUATION......Page 431
THE BALANCE OF ATHEROSCLEROSIS: THERAPEUTIC IMPLICATIONS......Page 432
SUMMARY......Page 433
REFERENCES......Page 434
INTRODUCTION......Page 437
PLASTICITY OF POSTNATAL STEM CELLS: IMPLICATIONS FOR CELL AND GENE THERAPIES......Page 438
MICROARRAY TECHNOLOGY......Page 443
SUMMARY......Page 445
REFERENCES......Page 446
Index......Page 448