Index

avβ3, 392 integrin, 356

α-adrenergic receptor, 294 β-adrenergic receptor, 294

β2-adrenoceptor subtype, 295 3-O-sulfotransferae (3OST), 127 17β-estradiol, 389 20-hydroxyeicosatetraenoic acid

(20-HETE), 296

26S proteasome, 182

aberrant sprouting of intersomitic vessel, 49

acetylcholine, 295, 387, 388

acute myocardial infarction, 264, 410 Ad5NOS-III, 399

AdCA5, 185, 187 adeno-associated virus, 393 adenosine, 293

adenovirus, 393

adenoviral delivery, 404 AdLacZ, 407 AdNOS1177D, 407 AEE788, 329

AG-013736, 329

age-dependent impairment, 400, 402 aging process, 301, 400

Akt, 183, 229, 389 Akt-KO mice, 403

Akt-1-KO mice, 407, 408 Akt-phosphorylated wild-type

NOS-III enzyme, 403 AMG 706, 330

angiogenesis, 109, 110, 175, 184, 186, 198, 217, 219, 220, 225, 229, 253, 260, 385, 389, 391, 397

angiogenesis-dependent transcription factor, 233

corneal, 391 coronary, 407 impaired, 400 ischemia–induced, 406 post-ischemic, 401 postnatal, 51, 226 therapeutic, 343, 395

tumor, 67, 75, 105, 107, 198, 313, 390 repair associated, 78

angiogenic

growth factor, 305 therapy, 370 response, 217

angiography, 198 evidence, 399

angiopoietin-1 (Ang-1), 218, 223, 230, 232

angiopoietin-2 (Ang-2), 185, 367 angiostatin, 409

angiotensin II (Ang II), 218, 223, 227 type 1 receptor, 266

angiotensin-converting enzyme (ACE) inhibition, 256, 389

animal model, 396

ankle brachial index (ABI), 372 anti-angiogenic

effect, 200

kinase inhibitor, selectivity of, 315 anti-cancer agent, 200

anti-CD31 immunohistochemistry, 198 antioxidant, 220, 221

vitamin, 389 aortocaval fistula, 258 Apo E-KO mice, 392

424 Index

apolipoprotein-E deficient (ApoE−/−) mice, 234

apoptosis, 217, 300, 402 cardiac myocyte, 409

arterial occlusion rabbit model, 197 arterial-venous capillary boundary

formation, 45

arteriogenesis, 101, 175, 186, 198, 253, 260, 344, 397, 406

arteriolar length density, 258 asymmetric dimethylarginine (ADMA),

302, 391

atherosclerosis, 95, 218, 228, 301, 386 atherosclerotic plaque, 105

ATP, 176

atrial natriuretic peptide (ANP), 223, 290 autoimmune disease, 394 autoregulation, 286, 292

axon guidance factor, 4 AZD 2171, 330

balb/c mice, 406

BAY 43-9006 (Sorafenib), 326 bcl-2, 369

BIBF 1120, 330

blood pressure (BP), 198, 388 blood vessel permeability, 327

bone marrow-derived mononuclear cell (BM-MNC), 348

brain natriuretic peptide (BNP), 290 Buerger disease, 372

c-kit, 330 c-met, 367, 368

Ca2+-activated K+ (BK) channel, 296

Caenorhabditis elegans, 176 cancer drug, 313

capillary, 282 angiogenesis, 100

capillary: myocyte ratio, 198 capillary growth, 263

inadequate, 256

cellular adenoviral receptor (CAR), 394 cardiac hypertrophy, 253, 255, 306

model, 254 cardiomyocyte, 226

cardiovascular disease, 387

gene transfer, 393 system, 367

catalase, 221

CBP co-activator, 183 cell migration, 4

cerebral artery occlusion, 388 chemokine, 120

Chir-258, 330 cholinergic receptor, 295

chorioallantoic membrane (CAM) model, 221

chronic heart failure, 410 clinical trial, 348

collapsin response mediator protein-2 (CRMP-2), 12

collateral formation, 375 collateral growth, 409

ischemia-induced, 407 collateral vessel, 303, 399

arterialized, 393 development, 395

colorectal cancer, 326 congestive heart failure, 387 converting enzyme, 97

copper/zinc SOD (Cu/ZnSOD), 222 cytosolic, 219

coronary flow, 253 regulation, 283

coronary reactive hyperemia, 260 coronary reserve, 255, 263

decline, 255 coronary resistance, 283

coronary vascular tone, 281 critical closing pressure, 299

critical limb ischemia (CLI), 370, 395 mouse model, 406

crosstalk, endostatin-VEGF, 40 cyclic guanidine monophosphate

(cGMP), 288, 386, 391, 410 c-GMP-dependent protein kinase,

288 cyclooxygenase, 219 cytochrome p450, 219

diabetes, 218, 228, 301, 387 diastolic stress, 258

dipeptidyl peptidase IV (DPPIV), 97 docetaxel, 328

Drosophila melanogaster, 176

electron transfer, 177 embryonic development, 367

endocardial/epicardial flow ratio, 258 endostatin, 403

endothelial

capillary morphogenesis, 33 factors in vascular growth, 300 function, 387

NO production, 288 senescence, 360

endothelial cell (EC), 185, 217, 256, 281, 368, 397

adhesion, 98 arterial, 187 capillary, 393

coronary post-capillary (venular), 409

cultured, 389 differentiation, 98

dysfunction, 228, 303, 359, 387, 406 human microvascular, 220 migration, 98, 222, 392

precursor, 396

proliferation, 95, 98, 222, 316, 391, 392

endothelial nitric oxide synthase (eNOS), 98, 219, 229, 287, 301, 386, 410

eNOS/NO pathway, 232 gene transfer, 385 protein expression, 404

endothelial progenitor cell (EPC), 228, 301, 347

endothelin, 287 endothelin-1, 184, 299

endothelium, 287 endothelium-dependent relaxation,

305, 389 endothelium-dependent

vasodilation, 387, 389 impaired, 303

Index 425

endothelium-derived hyperpolarizing factor (EDHF), 290, 293

endothelium-derived NO (EDNO), 386 overexpression, 410

deficiency, 387, 411 endothelium-derived relaxing factor

(EDRF), 385 endothelium-specific kinase, 314 endurance training, 263

EPAS1 gene, 181 Eph, 156

family, 27 receptor, 28

EphA receptor, 27 EphA2, 59

attractive target for selective antiangiogenic therapy, 59

signaling in endothelial cell migration and vascular assembly, 34

EphB, 35 receptor, 27

EphB4, 44, 315

venous endothelial cell marker, 44 ephrin, 156

ephrin-A1, 28, 33 ephrin-B, 35

ephrin-B reverse signaling, 37 angiogenic effect, 38

ephrin-B2, 44

arterial endothelial cell molecular marker, 44

epicardial coronary artery, 297 epidermal growth factor (EGF), 230 epoxyeicosatrienoic acid (EET), 290 ERK, 184

ERK-STAT3 pathway, 369 erythropoietin (EPO), 178

Ets

Ets-1, 233, 376

family of transcription factors, 375 pathway, 375

extracellular matrix, 217 extracellular SOD (ecSOD), 219 extravascular force, 297

fetal heart, 269

426 Index

fibroblast growth factor (FGF), 67, 77, 390, 392, 396, 410

administration, 79 FGF-1, 305

FGF-2, 98, 266, 305, 377, 392 fibroblast growth factor receptor

(FGFR), 133 soluble, 76

fibrosis, 266 fibstatin, 77

flow-induced dilation, 287, 292 Flt-1, 229

forward signaling, 158

Gab1, 369 gain-of-function study, 186

gastrointestinal stromal tumor (GIST), 327

Gefitinib, 329

gene delivery vector, 393 gene therapy, 355

glycosylphosphatidylinositol (GPI) linkage, 29

glypican, 68

granulocyte macrophage colonystimulating factor (GM-CSF), 355

Grb-SOS complex, 369 green tea catechin, 229 growth factor, 201 GTPase, 155

GTPase activating protein (GAP)- like domain, 5

guidance cue, 147 GW786034, 331

heart, 407 failure, 218

hemodynamic force, 271

heparan sulfate proteoglycan (HSPG), 68, 119

heparin, 121

heparin-binding growth factor, 121 hepatocyte growth factor (HGF), 315,

367, 390, 396, 410

gene therapy for myocardial ischemia, 375

plasmid DNA, 371 signaling, 368

herparan sulfate (HS)

development, 131

Hif1aflox/flox; Tie2-Cre mice, 186 HIF-α, 262

HIF-1α, 99, 179, 198, 233

O2-dependent degradation, 182 transactivation domain, 183

HIF-1β, 179 HIF-2αs, 181 HIF-3α, 182 hindlimb

blood flow, 397 ischemia, 403

histone acetyltransferase, 181 humoral substance, 294

Homo sapiens, 178

hydrogen peroxide (H2O2), 217, 219, 220, 232, 293

hydroxyl radical (•OH), 219 hyperglycemia, 228, 394, 403 hyperlipidemia, 301 hyperoxia, 177 hyperpolarizing factor, 287

hypertension, 218, 254, 255, 303, 330, 368 hypertensive reaction, 334

hypertrophy

exercise induced, 263 hypoxia induced, 261

myocardial infarction induced, 264 pressure overload induced, 255 right ventricular, 256

thyroxine induced, 260

volume overload induced cardiac, 258

hypochlorous acid (HOCl), 219 hypoxia, 137, 177, 181, 184, 187, 201, 220,

288

hypoxia-inducible factor-1 (HIF-1), 175, 178, 185, 186, 233

hypoxia response element (HRE), 178 binding site, 178

target gene, 204

IGF-R1, 201

immune response, 394 regulation of, 92

inducible nitric oxide synthase (iNOS), 221, 386

inhibitory PAS (IPAS), 182 insulin-like growth factor (IGF)-2, 202 intrinsic

control mechanism, 285 myogenic tone, 296

ischemia, 297

ischemia-induced myocyte death, 410 ischemia-induced retinal neovascu-

larization, 192 ischemia-reperfusion, 303 ischemic heart disease, 375 ischemic ulcer, 373

jagged1, 70

KDR expression, 401 KDR/Flk1, 229 kinase inhibitor, 313

L-arginine, 391

left ventricular end diastolic volume, 261 lentivirus, 393

limb loss, 400, 405 liposome, 393

L-nitroarginine methyl ester (L-NAME), 300, 392, 409

loss-of-function study, 186 lovastatin, 389

low density lipoprotein (LDL), 394

macrophage, 218, 220

magnetic resonance imaging (MRI), 357 maximal vasodilation, 254

metabolic regulation, 286

matrix metalloproteinase (MMP), 234, 409

MMP-1, 376

MMP-2, 409

MMP-9, 409 metastatic

breast cancer, 328

neuroendocrine tumor (NET), 327

Index 427

micro-CT, 356 microangiography, 399

microcirculation, neurohumoral influence on, 294

microvascular physiology, 281

resistance, redistribution of, 284 microvessel

arterial, 282 classification, 281 venous, 283

minimal coronary vascular resistance, 254

mitochondria, 176 mitochondrial-

restricted manganese SOD (MnSOD), 219

mitogenic effect, 97 monocyte, 218

monocyte chemoattractant protein (MCP)-1, 233

mouse, 388 mTOR, 183

myeloperoxidase (MPO), 219 myocardial blood flow, 258

redistribution, 258 myocardial

gene transfer, 409 ischemia, 388 perfusion, 254

N-acetylcysteine (NAC), 221

NG -monomethyl-arginine (L-NMMA), 389

Na/K ATPase, 290

NAD(P)H oxidase, 218, 222, 224, 225 phagocytic, 222

vascular, 222 naked plasmid, 393

Nck-NIK-JNK pathway, 36 neointima, 105, 387 neovascularization, 95, 192, 344 nerve conduction velocity, 378 neural crest origin, 109 neuroblastoma, 106

growth factor, 107

428 Index

neurogenesis, 109, 110 neurogenic trophic factor, 92 neuronal

precursor, 107 sprouting, 110 neuropeptide Y, 91, 296

neuropilin, 314 neuropilin-1, 148

neuronal nitric oxide synthase (nNOS), 386

neurotransmitter, 294 release, inhibition of, 92

nitric oxide (NO), 98, 232, 287, 293, 300, 334, 359, 377, 385, 395, 410

donor, 393 nitroglycerin, 409 NO•, 219, 288

NOGA™ system, 375

non-insulin diabetes mellitus (NIDDM) rat model, 227

non-obese diabetic (NOD) mice, 403, 406, 408

non-small cell lung cancer (NSCLC), 327 non-viral vector, 393

NOS gene transfer, 393 NOS-II gene transfer, 394 NOS-III, 387, 410

adventitial delivery, 394 gene transfer, 394 genetic deficiency, 406 mutant gene, 401, 402

NOS-III-deficient mice, 388 NOS-III-KO mice, 391, 396, 402 NOS-III-S1177D gene transfer, 403 phosphomimetic mutant, 411 serine 1177 in enzyme, 390 transgenic mice, 397

wild-type enzyme, 402 wild-type gene transfer, 401

NOS1177D, 402 notch, 70, 132 Nox2, 226

knockout mice, 226

oxygen (O2)

atmospheric concentration, 176

consumption, 177 delivery, 176 diffusion, 176, 254 homeostasis, 175, 177 utilization, 253

old animals, 400 organogenesis, 367 oxidative

phosphorylation, 176 stress, 218, 302, 360

oxidatively modified LDL (oxLDL), 386, 403

p22phox, 222

transgenic mice overexpressing, 226 p300, 183

p40phox, 222 p47phox, 222 p67phox, 222

paclitaxel/carboplatin, 328 parasympathetic nervous system, 294 PDGFR-β kinase, 326

PECAM-1, 397

percutaneous revascularization, 370 pericyte, 204

peripheral arterial disease (PAD), 370 clinical trial, 371

peripheral arterial occlusive disease, 387, 395

peripheral blood-derived mononuclear cell (PB-MNC), 348

peripheral neuropathy, 378 perlecan, 68

peroxynitrite (ONOO−), 219 phagocyte, 218 pharmacokinetics, 354 phase II study, 326

phase III trial, 326 pheochromocytoma, 108 phosphatidylinositol-3-OH kinase

(PI3K), 369 photosynthesis, 176 PI3K-Akt pathway, 369

pigment epithelium-derived factor (PEDF), 221

placebo effect, 358

placental growth factor (PLGF), 185, 192 plasmid, 403

plasminogen activator inhibitor-1 (PAI-1), 234

platelet-derived growth factor (PDGF), 315

PDGF-B, 185

PDGF-BB, 270 plexin D1, 151

positron-emission tomography (PET), 357

post-ischemic

flow recovery, 405 revascularization, 391

postsynaptic density 95, disk large, zona occludens-1 (PDZ), binding motif, 6, 154

pre-immunized pig, 409 progenitor cell, 42 prostacyclin synthase, 378 prostaglandin, 287

prostaglandin I2 (PGI2), 290, 377 prostate cancer, 228

protein tyrosine phosphatase, 230 PTK/ZK (Vatalanib), 326 pulmonary artery coarctation, 254

QT interval prolongation, 328 quinapril, 389

Rac1, 222

Raf-1, 326 rapamycin, 183

Ras-MAP kinase cascade, 369

reactive oxygen species (ROS), 217, 218, 222, 287, 360

molecular target, 230

receptor tyrosine kinase family V, 316 red wine, 221

redox

signaling, 229 state, 217

renal cell carcinoma (RCC), 326 renin-angiotensin system, 227 reoxygenation, 181

reperfusion injury, 388

Index 429

restenosis after angioplasty, 377 resting pain, 373

retinal neovascularization, 221 retinopathy, 103, 104

reverse signaling, 160

Rho guanine exchange factor (GEF), 155

Sef, 72

sema domain, 4 sema3C, 151 sema3E, 151

semaphorin signaling, 148 sepsis, 394

serotonin, 299 Shc, 369

shear stress, 286, 288, 393, 402 single-photon emission computed

tomography (SPECT), 357 skin ulcer, 400

smooth muscle cell, 281

soluble guanylate cyclase (sGC), 386 split kinase domain, 316 spontaneously hypertensive rat, 256 Src family kinases, 38

STAT pathway, 369 statin, 227, 389 stem cell, 42

stromal-derived growth factor-1 (SDF-1), 185

SU11248 (Sunitinib), 327

SU5416 (Semaxinib), 331 subendocardial infarct, 285 substance P, 296

Sulf1, 138

Sulf2, 138

superoxide anion radical (O•2−), 217, 219, 302, 386

superoxide dismutase (SOD), 221 sympathetic nervous system, 294 syndecan, 68

syndecan-1, 41

synergism, FGF and VEGF, 77

telomere, 360 tempol, 221 therapeutic trial

430 Index

for coronary disease, 79

for intermittent claudication, 79 Tie-1, 314

Tie-2, 262, 266 Tie-2 receptor, 230 tissue edema, 297

transcutaneous PO2 (TcPO2), 372 transforming growth factor (TGF)-α,

202 TGF-β, 367

tumor cell proliferation, 316 tumor vasculature, 54 tyrosine phosphorylation, 368 tyrosine-kinase Fes/Fps, 5

ubiquitination, 182

urokinase plasminogen activator (uPA), 234, 392

vagal stimulation, 295 vascular

cell, 367 growth, 254 injury, 300

permeability, 198 remodeling, 95 resistance, 254 tone, 388

vascular cell-adhesion molecule-1 (VCAM-1), 233

vascular endothelial growth

factor (VEGF), 1, 40, 77, 179, 192, 200, 204, 217–219, 223, 225, 227, 256, 262, 266, 301, 305, 328, 373, 389, 391, 392, 396, 400, 409, 410

gene, 184 polymorphism, 361 signaling, 134 VEGF-121, 392 VEGF-165 gene, 377 VEGF-A, 314

VEGF-C, 314

VEGF-D, 314 VEGF/KDR, 389

vascular smooth muscle cell (VSMC), 47 migration, 373

proliferation, 97 vasculature, 218 vasculogenesis, 267, 346 vasoconstriction, 92

effect, 97

vasomotor tone, endothelial regulation of, 286

vasopressin, 299

VEGF receptor (VEGFR), 201, 270, 314, 401

tyrosine kinase, 327, 328 VEGFR-1, 229 VEGFR-2, 98, 184, 229

ventricular remodeling, 410 viral vector, 393

volumetric computed tomography (VCT), 357

von Hippel-Lindau (VHL)

null renal carcinoma cell, 179 tumor suppressor protein, 182 von Willebrand factor (vWF), 401

white adipose tissue (WAT), 102 wound

healing, 101 repair, 101

xanthine oxidase, 218

Y1 receptor, 94, 95

Y1/Y5 receptor, 97

Y2 receptor, 95

Y2/Y5 receptor, 97

ZD6474, 328