INDEX
349 A
ACE inhibitors, see Angiotensin- converting enzyme inhibitors Adenosine,
coronary microcirculation effects, 94
vasomotor tone regulation, 71, 72 Adrenergic receptors, vasomotor
tone regulation, 73, 74 Ameroid constrictor models,
advantages, 44
clinical utility prospects, 59, 60 constrictor structure and
mechanism, 40, 42, 43 disadvantages, 44
electromechanical left ventricular mapping, 58, 59
imaging, 46, 55–57 rabbit model, 44, 45
Angiogenesis, see also Therapeutic angiogenesis,
definition, 4, 108, 186 development, see
Vasculogenesis embryonic stem cell
transplantation studies, 296–298
induction in myocardial ischemia, 4
inflammation and induction, 23, 24
transcriptionally mediated hypoxia responses, 22, 23 transmyocardial laser
revascularization, 341
Angiotensin-converting enzyme (ACE) inhibitors, coronary microcirculation effects, 94, 95 Animal models,
cell therapy studies, 54, 55 collateral circulation, 38, 39 coronary circulation anatomy, 38 delivery systems, see Gene
therapy; Myocardial delivery
growth factor therapy studies, 49–51
hindlimb ischemia model, 48 myocardial ischemia,
ameroid constrictor models, advantages, 44
constrictor structure and mechanism, 40, 42, 43
disadvantages, 44 rabbit model, 44, 45 cryothermia-induced
myocardial infarction, 46, 47
infarction, 40
intermittent occlusion model, 45
ligation myocardial infarction, 48 microembolization model,
47, 48
minimally invasive coronary stenosis model, 46 Vineberg direct arterial
implantation, 45, 46
pig vs dog, 38, 39 selection criteria, 38
skeletal myoblast transplantation studies, 314–316
ARNT, angiogenesis control, 22 Arteriogenesis,
collateral vessel formation, 217 definition, 4, 6
Atherosclerosis, microcirculation dysfunction, 83
B
Bone marrow cell transplantation, clinical trials, 271, 272, 275, 276 complications, 276
cytokine regulation of cells, 264, 265
delivery, 268–271
myocardial regeneration, 265–267 prospects, 276, 277
stem cell features, 262, 264 therapeutic angiogenesis, 268 C
CABG, see Coronary artery bypass grafting
CAD, see Coronary artery disease Calcium channel blockers, coronary
microcirculation effects, 94 Calcium flux, myogenic tone
regulation, 68, 69 Cardiopulmonary bypass,
microcirculation dysfunction, 84, 85
CBP, see CREB-binding protein Cell therapy, see Bone marrow cell
transplantation; Embryonic stem cells; Skeletal myoblast transplantation
CHF, see Congestive heart failure Cilostazol, peripheral artery disease
management, 247, 248 Computed tomography (CT),
animal model imaging, 56, 57
comparison of imaging techniques, 145 Congestive heart failure (CHF),
epidemiology, 2
heart transplantation, 283, 284, 312
Coronary artery bypass grafting (CABG), no-option patients, 3, 185, 186, 329
Coronary artery disease (CAD), see also Atherosclerosis;
Myocardial infarction, economic impact, 2 epidemiology, 261 mortality, 1
no-option patients, 3, 107, 185, 186, 262
Coronary microcirculation, components, 66
coronary resistance circulation as defined by pressure gradients, 66, 67 endothelial factors in vascular
growth, development, and injury response, 77–79 growth factor acute effects, 87,
89–91 pathophysiology,
atherosclerosis, 83 cardiopulmonary bypass,
84, 85
collateral vessel development, 85, 87
hypercholesterolemia, 82, 83, 87
pharmacology, 91–95 prospects for study, 95, 96 vasomotor tone regulation,
endothelial regulation, 74–76 extravascular forces, 72, 73 humoral agent control, 74 metabolic regulation and
autoregulation, 70–72
myogenic tone, 68–70 neurohormonal control, 73, 74 venules and overall coronary
vascular responsiveness, 76, 77
CREB-binding protein (CBP), angiogenesis control, 23 Critical limb ischemia, see
Peripheral artery disease CT, see Computed tomography D
Delivery systems, see Gene therapy; Myocardial delivery systems
dHAND, smooth muscle cell differentiation role, 27, 28 Direct intramyocardial injection,
therapeutic angiogenesis, 52, 53, 111–113
Dyslipidemia,
endothelial dysfunction, 9 microcirculation dysfunction, 82,
83, 87
EECP, see Enhanced external counterpulsation
Electromechanical left ventricular mapping, 58, 59, 229, 271 ELF-1,
angiogenesis control, 21 hematopoiesis and endothelial
control, 29 Embryonic stem cells,
cardiomyocyte differentiation, culture conditions, 285, 286 factors influencing, 286,
288–290 cellular cardiomyoplasty,
aging heart, 294 angiogenesis, 296–298 immune tolerance, 301–303 myocardial infarction studies,
291–293
myocardial regeneration, 295, 296
myocarditis, 293, 294 overview, 284 prospects, 303–305 characterization, 285 homing studies after
transplantation, 298–301 plasticity, 284, 285
Endothelin-1 (ET-1), vasomotor tone regulation, 74 Endothelium-derived
hyperpolarizing factor (EDHF), vasomotor tone regulation, 76
Enhanced external counterpulsation (EECP), efficacy in no-option patients, 11
EPAS1, angiogenesis control, 22 ESE-1, angiogenesis control, 24 ET-1, see Endothelin-1
ETS-1, angiogenesis control, 21 F
FGFs, see Fibroblast growth factors Fibroblast growth factors (FGFs),
clinical studies of myocardial angiogenesis,
intracoronary and intravenous FGF-2, 200, 201 intramyocardial FGF-1, 197 periadventitial FGF-2 with
slow-release beads, 197, 200
delivery systems, see Gene therapy; Myocardial delivery systems endothelial responses, 188 FGF-2,
animal model studies, 49–51 coronary microcirculation
acute effects, 87, 89–91 forms used in clinical trials, 188
functional overview, 219 gene therapy,
myocardial ischemia trials, 232–234
peripheral vascular disease trials, 231, 232 sequence modifications, 219 preclinical studies of myocardial
angiogenesis, 189–192, 195 protein therapy versus gene
therapy, 202–205 types, 219, 249 Flk-1,
endothelial differentiation role, 25 ischemia induction, 79
Flt-1, ischemia induction, 79 Fra1,
angiogenesis control, 24
endothelial differentiation role, 25 G
Gene therapy,
delivery in animal models, catheter-based
transendocardial injection, 52 intracoronary delivery, 54 intramyocardial injection, direct injection, 52, 53 thoracotomy, 51, 52 intrapericardial delivery,
53, 54
fibroblast growth factors, myocardial ischemia trials,
232–234
peripheral vascular disease trials, 231, 232 sequence modifications, 219 prospects, 235–237
protein therapy vs gene therapy, 202–205
safety concerns, 234, 235
vascular endothelial growth factor,
advantages, 218, 219 myocardial ischemia trials,
224–230
peripheral vascular disease trials, 220–223 restenosis prevention after
peripheral angioplasty, 223, 224
stent restenosis prevention trials, 230, 231 viral vs nonviral gene transfer
systems, 220, 251 H
HESR1, endothelial tube formation role, 26
HIF-1F, see Hypoxia-induced factor-1F
HMG-CoA reductase inhibitors, see Statins
Hox D3,
angiogenesis control, 24 endothelial tube formation role,
26
Hypoxia-induced factor-1F (HIF- 1F), angiogenesis control, 22, 23
I
Intermittent claudication, see Peripheral artery disease Intracoronary delivery, therapeutic
angiogenesis, 54, 121–123 Intrapericardial delivery,
therapeutic angiogenesis, 53, 54, 118, 119, 121
K
KATP channels,
pharmacological modulation, 94 vasomotor tone regulation, 71, 72
L LKLF,
angiogenesis control, 24 smooth muscle cell
differentiation role, 26, 27 M
Magnetic resonance imaging (MRI),
angiogenesis-sensitive imaging, 160–162, 164, 167
animal model imaging, 46, 55, 56 cell tracking, 148, 149
collateral-sensitive imaging in swine, 56, 57
comparison of imaging techniques, 145 molecular imaging, 149
perfusion-sensitive imaging, 151, 154, 155, 157, 158, 160 small animal angiogenesis
imaging, 174–177 MAPK, see Mitogen-activated
protein kinase
MEF2C, smooth muscle cell differentiation role, 26 MI, see Myocardial infarction Microcirculation, see Coronary
microcirculation
Mitogen-activated protein kinase (MAPK), myogenic tone regulation, 70
MRI, see Magnetic resonance imaging
Myoblast, see Skeletal myoblast transplantation
Myocardial delivery systems, bone marrow cell
transplantation, 268–271 comparison of techniques,
126–129
direct intramyocardial injection, 111–113
gene therapy delivery in animal models,
catheter-based transendocardial injection, 52 intracoronary delivery, 54 intramyocardial injection, direct injection, 52, 53 thoracotomy, 51, 52 intrapericardial delivery,
53, 54 ideal criteria, 108, 109
intracoronary delivery, 121–123 intrapericardial delivery, 118,
119, 121
percutaneous intramyocardial delivery, 113–116, 118 perivascular delivery, 118, 119,
121
prospects, 129, 130
protein growth factors, 205–207 retrograde coronary venous
delivery, 123–126 systemic cardiac delivery,
108–111
Myocardial infarction (MI), animal models, 40, 46–48 embryonic stem cell
transplantation studies, 291–293
epidemiology, 311 scarring, 311, 312 Myocardial ischemia,
angiogenesis induction, 4 animal models,
ameroid constrictor models, advantages, 44
constrictor structure and mechanism, 40, 42, 43
disadvantages, 44 rabbit model, 44, 45
cryothermia-induced myocardial infarction, 46, 47
infarction, 40
intermittent occlusion model, 45
ligation myocardial infarction, 48 microembolization model,
47, 48
minimally invasive coronary stenosis model, 46 Vineberg direct arterial
implantation, 45, 46 transcriptionally mediated
hypoxia responses, 22, 23 N
NERF,
hematopoiesis and endothelial control, 29, 30
isoforms, 29, 30
Nitrates, coronary microcirculation effects, 92
Nitric oxide (NO),
angiogenesis role, 79–82 synthases, 75
vascular growth, development, and injury response role, 77–79
vasomotor tone regulation, 75, 76
NO, see Nitric oxide P
PAD, see Peripheral artery disease PCI, see Percutaneous coronary
intervention
Pentoxifylline, peripheral artery disease management, 247 Percutaneous coronary intervention
(PCI), no-option patients, 3, 107, 185, 186, 329
Percutaneous intramyocardial delivery, therapeutic angiogenesis, 113–116, 118 Peripheral artery disease (PAD),
anatomy, 247
angiogenic response to limb ischemia, 252
epidemiology, 246 management, 247, 248 pathophysiology, 247 syndromes,
comparison, 246
critical limb ischemia, 247 intermittent claudication,
247
therapeutic angiogenesis, angiogenic agent delivery
systems, 251, 252 critical limb ischemia trials,
253, 254
fibroblast growth factor trials, 231, 232
intermittent claudication trials, 254, 255 preclinical studies, 252–254 prospects, 255, 256
vascular endothelial growth factor trials, 220–223 Perivascular delivery, therapeutic angiogenesis, 118, 119, 121 PET, see Positron emission
tomography
Positron emission tomography (PET),
comparison of imaging techniques, 145 functional imaging, 173, 174 molecular imaging, 149 principles, 173, 174 Prostanoids,
myogenic tone regulation, 69, 70 vasomotor tone regulation, 76
R
Ranolazine,
efficacy in no-option patients, 13 metabolic modulation, 11–13 RAVE trial, findings, 255 Retrograde coronary venous
delivery, therapeutic angiogenesis, 123–126 REVASC trial, findings, 228 S
SCS, see Spinal cord stimulation Serial Motion Assessment by
Reference Tracking (SMART), functional imaging, 169, 178 Shape index (SI), micrograph
analysis, 146, 147 SI, see Shape index
Single photon emission computed tomography (SPECT), animal model imaging, 46, 55, 56 comparison of imaging
techniques, 145 principles, 170
technium-99m sestamibi scans, 170, 172, 173
thallium-201 uptake, 170–173 Skeletal myoblast transplantation,
advantages, 313, 314 clinical trials, 318–322
mechanisms of action, 320, 323 myoblast features, 313, 314 preclinical studies,
animal models, 314–316 cardiomyocyte
differentiation, 317 cell integration into host
myocardium, 317, 318 cell survival, 314, 317 functional improvement
outcomes, 318 prospects, 323–325
SMAD5, smooth muscle cell differentiation role, 26 SMART, see Serial Motion
Assessment by Reference Tracking
Spinal cord stimulation (SCS), efficacy in no-option patients, 10, 11
Statins,
coronary microcirculation effects, 95
peripheral artery disease management, 247 Stem cells, see Bone marrow cell
transplantation; Embryonic stem cells
T
Technium-99m sestamibi scans, 170, 172, 173
Therapeutic angiogenesis, see also Gene therapy,
cancer concerns, 144 cell therapy, see Cell therapy delivery systems, see Gene
therapy; Myocardial delivery systems endothelial dysfunction in
dyslipidemia, 9 growth factors, see specific
factors
ideal criteria for agents, 186, 187 peripheral artery disease, see
Peripheral artery disease, rationale, 4
Tie2, transcription factors in gene regulation, 31
TMR, see Transmyocardial laser revascularization
TNF-F, see Tumor necrosis factor-F TRAFFIC trial, findings, 255 Transmyocardial laser
revascularization (TMR),
clinical trials, 330
historical perspective, 329 laser modalities and outcomes,
334–338 mechanisms of action,
angiogenesis, 341 denervation, 338, 341 laser–tissue interaction, 337,
338
patent channels, 338 operative technique, 330, 331 outcomes,
angina class, 333 endpoints in trials, 332 exercise tolerance, 334 hospital admission, 334 long-term results, 335–337 medication reduction, 335 morbidity, 333
mortality, 332, 333
myocardial perfusion studies, 335
quality of life, 333, 334 patient selection, 330 percutaneous treatment and
placebo effect, 342 prospects, 342, 343 Trimetazidine,
efficacy in no-option patients, 13 metabolic modulation, 11–13 Tumor necrosis factor-F (TNF-F),
embryonic stem cell homing role, 298–300
myocardial injury role, 298 V
Vascular endothelial growth factor (VEGF),
animal model studies, 49–51 coronary microcirculation acute
effects, 87, 89–91
delivery systems, see Gene therapy; Myocardial delivery systems endothelial responses, 187,
188 gene therapy,
advantages, 218, 219 myocardial ischemia trials,
224–230
peripheral vascular disease trials, 220–223 restenosis prevention after
peripheral angioplasty, 223, 224
stent restenosis prevention trials, 230, 231 intracoronary and intravenous
VEGF165 clinical studies of myocardial angiogenesis, 201, 202
isoforms, 187, 218, 249 nitric oxide relationship in
angiogenesis, 80, 81 preclinical studies of myocardial
angiogenesis, 193–97 protein therapy vs gene therapy,
202–205
receptors, see Flk-1; Flt-1 transcription factors in gene
regulation, 31 Vasculogenesis,
definition, 4, 217, 248 overview, 217 transcription factors,
animal models, 20, 21 clinical implications, 31, 32 conservation in vascular
development, 21 targeted disruption studies, 24 temporal and spatial aspects,
29, 31
VEGF, see Vascular endothelial growth factor
Vezf1, endothelial differentiation role, 25
VIVA trial, findings, 225
X
X-ray angiography (XRA), small animal angiogenesis imaging, 177
XRA, see X-ray angiography
