Index

Note: Page numbers followed by f indicate figures, and t indicate tables.

A genetic modification of stem cells, 272 neuroprotection, 201–202

AAVs. See Adeno-associated viruses (AAVs) heptapeptide, 156f oral delivery, 272
ACE. See Angiotensin-converting enzyme historical perspective, 225 PAH, 270
(ACE) inflammatory mediators, 250 PF, 270–271
ACE2. See Angiotensin-converting enzyme 2 insulin signaling system, 250–251, 251f physical exercise (see Physical exercise)
(ACE2) inventions, 157 in pulmonary diseases, 270
Acute phase postmyocardial infarction liver metabolic effects, 252 renal diseases, 208–209
apoptosis, 43 lung cancer, 225–226 renal physiology, 207–208
bradykinin/nitric oxide system, 42 Mas and MAPK signaling, 174–175 rhACE2, 271
cardiac function, 41 Mas-knockout mice, 175 shedding activity, 187
effects, 41, 42f Mas receptor expression, 169, 170f substrate specificity, 185, 186, 186t
inflammatory response, 43 mechanisms of protection, 202–203 TGF-β signaling, 214–215
intracellular acidosis, 42–43 nanocarriers (see Liposomes) tissue fibrosis, 214
tissue regeneration processes, 43 neuroprotection and Ras, 201–202 translation, 203–204
Acute respiratory distress syndrome (ARDS), NO production, 173, 197 vasodeleterious effects, 269–270
269 oral delivery, 272 vasoprotective effects, 269–270
ADAM17, 220–221 oral formulation, 252 Angiotensin-converting enzyme (ACE)
Adeno-associated viruses (AAVs), 242–243 PAH, 270 Alzheimer’s disease, 186
Adenoviral transduction, 104 PF, 270–271 Drosophila, 185
Adiponectin, 250 prostate cancer, 227 inhibitors, 240
Adipose tissue protein angiotensinogen, 156f somatic, 185
ARBs, 119 proteomics, 171, 172f substrate specificity, 185, 186, 186t
AT2R-deficient mice, 120 in pulmonary diseases, 270 Angiotensin II receptor (AT2R)
C21, 120–121 renal diseases, 208–209 biased agonism model, 4
direct AT2R agonist, 120–121 renal physiology, 207–208 binding protein family, 3
pharmacological interventions, 120 Ser1177 and Thr495, 197 cardiac hypertrophy, 2
therapeutic modulation, 119 specific binding site, 157 CGP 42112, 11, 12–14, 14f
Agonist therapy TGF-β signaling, 214–215 CGP 42112A, 1
CGP42112A, 76 therapeutic agent, 252, 271–272 classical and protective arms, 1, 2f
extracellular matrix accumulation, 75 tissue fibrosis, 214 clinical indications, 5, 6f
fibrosis, 75 translation, 203–204 cognitive function (see Cognitive function)
inflammation, 74 unresolved issues, 175–176 compounds structure, 11, 12f
obesity/diabetes, 76 vascular action, 157 disadvantages, 4
oxidative stress, 75 vasoactive peptide, 155 drug development, 5, 6t
vasodilation and counteracting mechanisms, 76 vasodeleterious effects, 269–270 eplerenone, 11
Albumin, 76 vasodilatory effects, 197 EXP 655, 1
Alzheimer’s disease, 186 vasoprotective effects, 269–270 experimental approaches, 5
Ang-(1-7). See Angiotensin-(1-7) (Ang-(1-7)) Angiotensin AT1 receptor (AT1R), 4, 265. G protein binding, 3
Ang II-evoked blood pressure, 111, 112–113, See also Angiotensin II receptor (AT2R) in heart, 41
113f, 115f Angiotensin-converting enzyme 2 (ACE2). heart capillary endothelial cells, 2
Angiogenesis, 225–226 See also Mas homo and heterodimerization, 3
Angiotensin-(1-7) (Ang-(1-7)) activators, 271 human myometrium, 11–12, 13f
ACE inhibitors, 225 Alzheimer’s disease, 186 inflammation (see Inflammation)
activation, 250, 250f biological roles, 186 intimal proliferation model, 2
AKT, 171–173 cardioprotective role, 187 Kagawa test, 11
antiproliferative action of, 198 cellular recruitment and function, 214 kidney (see Renal disease)
baroreflex actions, 157 cytokine regulation, 213–214 little brother concept, 3
bradykinin vasodilation, 198–199 [des-Arg9]-bradykinin, 186 losartan (DuP 753), 1, 12–14
breast cancer, 226–227 gene expression, 187–188 men and women (see Sex differences)
cellular recruitment and function, 214 genetic modification of stem cells, 272 MI (see Myocardial infarction (MI))
clinical trials, 227–228 glycemic control, 219–220 natriuresis (see Natriuresis)
counterregulatory effects of, 170f mechanisms of protection, 202–203 nervous system (see Nervous system)
cytokine regulation, 213–214 multifunctional protein, 188 NG 108-15 cells, 5

293
294  Index

Angiotensin II receptor (AT2R) (Continued) metabolic effects, 23 AT2 receptor-binding protein (ATBP), 3
NO/cGMP system, 4 phosphotyrosine phosphatase activation, 23 AT2 receptor-interacting proteins (ATIPs)
nomenclature, 14 PLZF, 23–24 alternative promoter usage and exon splicing,
PC12W cells, 5 proapoptotic effects, 23 106
PD 123177, 1, 11, 14, 14f proliferation and differentiation, 25–26 animal studies, 104
PD 123319, 1, 4, 15 solved and unsolved issues, 28–29 cancer cell types, 103–104, 104t, 105t
physical protein interaction partners, 3 T-type calcium current modulation, 23 classical ACE/AngII/AT1 axis, 103
physiological functions, 3, 3f vasodilatory effects, 23 classical RAS generation, 103, 104f
PLZF, 3 Animal models CNK1, 105, 105f
proliferative/hypertrophic agent, 2 ACE2 models, 162–164 ERBB3, 105, 105f, 106
rat adrenal glomerulosa membranes, 11–12, 13f Ang-(1-7) models, 165 functional effects, 104, 105t
selective drug-like AT2R agonists, 136–137 blood pressure, 17–18 IHC, 104, 104t
stimulation (see Adipose tissue) cardiac disease, 18 ISH, 104, 104t
sympathetic outflow (see Sympathetic knock out (KO) animal models, 161 PCR, 104, 104t
outflow) Mas models, 164 PLZF, 105, 105f, 106
vascular remodeling (see Vascular modification, 19, 20t receptor subtypes, 103, 104f
remodeling) neural disease, 19 regulation, 103
Angiotensinogen (AGT), 250, 252 prolylcarboxypeptidase KO mice, 164–165 TIMP3, 105, 105f, 106
Angiotensin peptides renal disease, 19 transducing molecules, 105
bone marrow recovery, 288 transgenic animal models, 161, 163t AT2R knockout (AT2KO) mice, 74
hematopoietic stem cell transplant, 289 vascular disease, 18–19 Autoimmune disease, 100
mucosal/gastrointestinal recovery, 289 ANP/BNP receptor guanylate cyclase (GC-A/
NHP, 288, 288f NPRA), 23
phase 1 evaluation, with and without Anti-inflammatory effects, 23 B
neupogen, 289–290, 290f Antiproliferative effects, 23 Baroreflex function, 111, 112f
phase 2a study, breast cancer patients, 290 Aortic aneurysm, 93 Biased agonism model, 4
phase 2b study, recurrent ovarian cancer Apoptosis Biglycan, 193
patients, 291 acute phase postmyocardial infarction, 43 Bile duct ligation (BDL) model, 240
synergy and multilineage effects, 289, 290f MI, 43 Blood pressure (BP)
Angiotensin 2 receptor (AT2R) agonists vascular remodeling, 89–90 ACE inhibitors, 198–199
Ang II, selective agonists, 136–137 ARDS. See Acute respiratory distress syndrome Ang-(1-7), 197, 198f
animal pharmacology and toxicology (ARDS) antiproliferative action, 198
studies, 150 AT2 expression Mas-deficient mice, 197
cardiovascular protection, 152 blood pressure, 17–18 NO generation, 197, 198f
chemistry and manufacturing cardiac disease, 18 preclinical studies, 50–51, 50t
information, 150 modification, 19, 20t vasodilatation, 49–50
clinical protocols and investigator neural disease, 19 vasorelaxation, 49
information, 150 renal disease, 19 VSMCs, 198
clinical trials, 150–151, 150t vascular disease, 18–19 Bradykinin (BK) pathway, 35–36
dementia, 152 Atherosclerosis Brain
diabetic nephropathy, 152 antiatherogenic actions, 93 baroreflex control, 231–232, 232f
IPF, 151–152 AT2R antagonist PD123319, 92f, 93 central neurotransmitters, 232f, 234–235, 234f
MFS, 151 AT2R/ApoE-KO mice, 92, 93 glucose tolerance, 232, 232f
natriuresis, 152 chronic inflammatory disease, 92 glycemia, 232, 232f
nonpeptide, 132–136 inflammation, 98 HOMA score, 232, 232f
nonselective, 132–136 LDL receptor (LDLR)-KO mice, 92–93 hypertension, 231
preclinical testing, 149, 150t proinflammatory environment, 92, 92f immunostaining, 231, 232f
AT2R antagonists, 137–138 Athlete’s heart, 263 insulinemia, 232, 232f
spinal cord injury, 152 ATIPs. See AT2 receptor-interacting proteins molecular analysis, 232–233
stroke, 152 (ATIPs) normalized baseline MAP, 232, 232f
structure of, 131, 131f AT1R. See Angiotensin AT1 receptor (AT1R) reduced cardiac sympathetic tone, 232, 232f
type II diabetes/metabolic syndrome, 152 AT1R blockers (ARBs), 67, 119–120, 240 stimulation, 231–232, 232f
Angiotensin receptor signaling AT1R-AT2R cross talk Breast cancer, 226–227
anti-inflammatory effects, 23 BK/nitric oxide pathway, 36
antiproliferative effects, 23 counterregulatory activity, 35–36 C
apoptosis, 26 detection, 35 Cancer
CGP42112 antagonist, 24 functional significance, 36–37 ACE inhibitors, 225
cognitive effects, 23 homo/heterodimerization receptor, 36 ATIP (see AT2 receptor-interacting proteins
dimerization, 24–25, 24f in vitro and in vivo studies, 35 (ATIPs))
fibrosis, 27, 28f limitations, 35 breast cancer, 226–227
functional selectivity, 24 negative modulation, 35–36 clinical trials, 227–228
GC-A/NPRA inhibition, 23 sodium excretion and blood pressure control, historical perspective, 225
indications, 23 35–36 lung cancer, 225–226
inflammation, 26–27 AT2R. See Angiotensin II receptor (AT2R) prostate cancer, 227
 Index  295

Cancer-associated fibroblasts (CAFs), 226 nonpregnant uterus, 256–258, 257f cardiac function, 43–44
Cardiac fibrosis, 44 ovary, 255–256, 256f, 257f cardiac hypertrophy, 44–45
Cardiac hypertrophy, 44–45 pregnant uterus and placenta, 258 effects, 41, 42f
Cardiac remodeling, 191–192 Fibrogenic pathways extracellular matrix degradation, 45
Cardiovascular disease TGF-β signaling, 214–215 Left ventricular (LV) remodeling, 191
atherosclerosis, 98 tissue fibrosis, 214 Liposomes
heart failure, 98–99 Fibrosis, 27, 28f, 75, 214 advantage, 275
renal injury, 99–100 alopecia treatment, 277
stroke, 99 G characteristics, 275
Caudal ventrolateral medulla (CVLM), 231, Gastric cancer, 103–104 controlled drug release, 276
232–233, 234 Gel electrophoresis, 257f HPβCD, 278
Central nervous system (CNS) Glomerulosclerosis, 74 liposome encapsulation, 276
anti-inflammatory potential, 58 Glycemic control microinjection, 276–277
cell-specific expression, 57 ACE2 shedding, 220, 221f modification, 276
ion currents/channels regulation, 58 Ang-II signaling, 220 telemetry, 276
molecular mechanisms, 58–59 β-cell function and insulin sensitivity, 220, 220f therapeutic applications, 277, 277t
neuroprotective molecular mechanism, 58 ER stress, 220 Liver fibrosis
regenerative potential, 58–59 Mas deficiency, 219–220 ACE2-Ang-(1-7)-MasR axis, 241–242
species and age-dependent, 57 G protein-coupled receptors (GPCRs), 169–171 ACE inhibitors, 240
Chemokine, 192 α-smooth muscle actin (α-SMA) protein
Chronic obstructive pulmonary disease expression, 240, 242f
(COPD), 269 H Ang-(1-7) infusion, 240, 242f
Heart failure (HF), 263
Cognitive effects, 23 AT1R blockers, 240
Hematopoietic stem cell transplant, 289
Cognitive function beneficial effects, 240–241
Hepatic steatosis, 252
ischemia-induced neuronal injury, 67–68 circulating Ang II and Ang-(1-7) levels, 240,
High-grade astrocytoma, 103–104
neural damage, 67–68, 68f 241f
High-grade renal cell carcinoma, 103–104
receptor-associated protein, 69, 69f classic RAS, 239
2-Hydroxypropyl β-cyclodextrin (HPβCD), 278
receptor stimulation, 68–69 cultured HSCs, 240, 242f
Hypertension, 119, 263
stroke, 67 DIZE, 243
vascular dysfunction, 67–68, 68f GI tract, 245
Collagen synthesis, 89–90 I viral vectors, 242–243
Congestive heart failure (HF), 191, 193–194, 193f Immunofluorescence, 257f Losartan (DuP 753), 1, 11, 12f
CVLM. See Caudal ventrolateral medulla Immunohistochemistry (IHC), 104, 104t Lung cancer, 225–226
(CVLM) Inflammation Lymph node metastases, 103–104
Cyclic guanosine monophosphate (cGMP) atherosclerosis, 98
pathway, 90 autoimmune disease, 100
Cyclodextrin, 278 cytokine regulation and cellular recruitment, M
Cyclooxygenase-2 (COX-2), 225 213–214 Male reproductive system
fibrogenic pathways, 214–215 corpus cavernosum, 260
heart failure, 98–99 prostate, 259
D JAK-STAT signaling pathway, 97, 98f testis, 259, 259f
Dementia, 67, 152 MAPK. See Mitogen-activated protein kinases
NF-κB, 97
Diabetes, 250, 252 (MAPK) signaling
oxidative stress, 97–98
Diabetic nephropathy, 152 Marfan syndrome (MFS), 89, 151
renal injury, 99–100
Diminazene aceturate (DIZE), 243 Mas. See also Angiotensin-(1-7) (Ang-(1-7))
stroke, 99
Ductal and invasive breast carcinoma, 103–104 activation, 250, 250f
In situ hybridization (ISH), 104, 104t
Interferon regulatory factor 1 (IRF-1), 73–74 Ang II, 207
E Intracellular acidosis, 42–43 antisense and imprinted Igf2r gene, 156
Endogenous angiotensin peptides Investigational new drug (IND) application, 150 cardiac remodeling, 191–192
Ang 1-7, 143 In vitro fertilization (IVF), 256 cellular recruitment and function, 214
Ang 1-9, 143 central nervous system (see Brain)
Ang II, 141 clinical conditions, 209
Ang III, 142
J cytokine regulation, 213–214
JAK-STAT signaling pathway, 97, 98f experimental models, 208–209
Ang IV, 142
binding affinity, 141, 142t expression, 156–157
functional Ang II receptor, 155–156
Endoplasmic reticulum (ER) stress, 220 K genetic modification of stem cells, 272
Epidermal growth factor receptor ERBB3, 105, Kagawa test, 11
105f, 106 inflammatory mediators, 250
Kallikrein-kinin system, 202
Estradiol, 256 inflammatory phase, 192
Knock out (KO) animal models, 161
insulin signaling system, 250–251, 251f
inventions, 155
F L liver metabolic effects, 252
Female reproductive system Late-phase postmyocardial infarction Mas-deficient mice, 157
breast, 258–259 cardiac fibrosis, 44 maturation phase, 193–194
296  Index

Mas (Continued) extracellular matrix degradation, 45 P

mechanism, 155, 156f and HF, 191 PAH. See Pulmonary arterial hypertension
MI and HF, 191 IL-1β expression, 192 (PAH)
neuroprotection, 201–202 inflammatory response, 43 Paraventricular nucleus (PVN),
oral formulation, 252 intracellular acidosis, 42–43 231, 234
PAH, 270 tenascin C (TNC), 193 Penile fibrosis, 260
PF, 270–271 TGF-β, 193 Perindopril, 264
physical exercise (see Physical exercise) tissue regeneration processes, 43 Peripheral neuronal injury, 57–58, 59
proliferative phase, 193 Myofibroblasts, 191 Physical exercise
protection mechanisms, 202–203 ACEI/D polymorphism, 263–264
in pulmonary diseases, 270
receptor agonists (see Mas agonists) N ACE inhibitor captopril, 264
Nanoparticle injection, 104 angiotensin-(1-7) effects, 264–265
AT1 receptors, 207–208 AT1 antagonist losartan, 264
TGF-β signaling, 214–215 Natriuresis
Ang II metabolism, 82, 83f blood pressure control, 266
therapeutic strategies, 252 cardiac and musculoskeletal effects, 263
tissue fibrosis, 214 AT2R agonists, 152
compound 21 (C-21), 84–85 nonpharmacological treatment, 265
translation, 203–204 perindopril, 264
vasodeleterious effects, 269–270 counter-regulatory hormonal systems, 85–86,
85f pharmacological treatment, 265
vasoprotective effects, 269–270 postganglionic sympathetic neurons, 264
Mas agonists dopamine D1 receptors interactions, 83–84
hypertension, 84 protective effects, 263
Ang-(1-7)-CyD, 281–282 tissue perfusion, 264
AR234960, 284 induction, 82
insulin resistance, 84 Polycystic ovary syndrome, 257–258
AR244555, 284 Poly(ethylene) glycol (PEG), 276–277
AVE-0991, 283 nephron sites, 83
obesity, 84 Polymerase chain reaction (PCR),
CGEN-856S, 283 104, 104t
cyclized Ang-(1-7), 282–283 physiological significance, 83, 84
renal expression, 81–82 Portal hypertension
MBP7, 284 Ang-(1-7) infusion, 244
pharmacological approaches, 281, 282f signaling mechanisms, 83
Nervous system complications, 243
Mas/AT2 cross talk dose-dependent reduction, 244, 244f
Ang-(1-7), 181 CNS, 57, 58–59
multiple sclerosis, 61 HSCs, 243, 243f
dimerization partners within protective arm intrahepatic vascular resistance,
receptors, 182, 183f peripheral neuronal injury, 57–58, 59
spinal cord injury, 61 244, 244f
GPCRs, 181 RAS-mediated pathophysiological
Ras representation, 181, 182f stroke, 59–61
TBI, 61 changes, 243, 243f
Mas-related G-coupled receptor type D Splanchnic vasodilation, 244–245, 244f
(MrgD), 281 Neumega®, 287
Neurological disorders, 128–129 Postexercise hypotension (PEH), 263
Mas signaling pathways Postmyocardial infarction model, 27
Akt role in, 171–173 Neuronal injury
global ischemia, 57–58 Proapoptotic effects, 23
GPCRs and, 169–171 Progesterone, 256
MAPK signaling, 174–175 hypertrophic and amoeboid morphology, 57–58
middle cerebral artery occlusion, 57–58 Proliferator-activated receptor alpha
Mas-knockout mice, 175 (PPAR-alpha), 120
NO production, 173 morphometric analysis, 59
neuroregenerative potentia, 59 Proliferator-activated receptor gamma
proteomic-based findings, 171 (PPAR-gamma), 120
Rac1 role in, 171 osmotic minipumps, 59
sciatic nerve crush, 57–58, 59 Prolylcarboxypeptidase (PRCP), 164–165
receptor expression, 169, 170f Promyelocytic leukemia zinc finger (PLZF), 3,
RhoA role in, 175 Neuroprotection
definition, 57 23–24, 105, 105f, 106
unresolved issues, 175–176 Prostate cancer, 227
Menstrual cycle, 256, 257 stroke (see Stroke)
Neuroregeneration process, 57 Proto-oncogene, 155
Metabolic syndrome, 152, 252 Pulmonary arterial hypertension (PAH), 269
Metastasis, 227 Nitric oxide (NO)
pathway, 35–36 Pulmonary fibrosis (PF), 269
Microglia, 202–203
Microtubule-associated tumor suppressor production, 173
(MTUS1) gene, 23, 106 Nonhuman primate (NHP), 288, 288f R
Middle cerebral artery occlusion (MCAO), 57–58 Norepinephrine (NE), 234–235, 234f Reactive oxygen species (ROS), 75
Mitogen-activated protein kinases (MAPK) Norepinephrine transporter (NET), 234f, 235 Receptor for advanced glycation end products
signaling, 174–175 Nuclear factor kappa-B (NF-κB), 97 (RAGE) expression, 19
Multiple sclerosis, 61 Nucleus tractus solitarii (NTS), 231, 232–233 Renal disease
Myocardial infarction (MI) Ang-(1-7), 207
apoptosis, 43 O Ang II, 207
bradykinin/nitric oxide system, 42 Obesity AT2KO mice, 74
cardiac fibrosis, 44 agonist therapy, 76 clinical conditions, 209
cardiac function, 41, 43–44 etiologic factor, 119 experimental models, 208–209
cardiac hypertrophy, 44–45 natriuresis, 84 proximal tubule epithelial cells, 75, 76
effects, 41, 42f progression, 119 AT1 receptors, 207–208
 Index  297

renal AT2R expression, 73–74 MCAO, 202 V

renoprotective mechanisms (see Agonist microglial activation, 202–203 Vascular AT2R effects
therapy) nervous system, 59–61 antihypertensive effect, 52–53
signaling pathways, 74 neuroprotection, 201 and BP level, 50–51, 50t
Renal sympathetic nerve activity (RSNA), 111, NF-κB, 202 human data analysis, 51–52, 51t
112–113, 112f, 114f RAS manipulation, 201 vasodilatation effect, 49–50
RhoA, 175 risk factors, 203 vasorelaxation effect, 49
Rostral ventrolateral medulla (RVLM), 114f, treatment, 203 Vascular endothelial growth factor (VEGF),
115f, 116f, 231, 232–233, 234, 264 Supraoptic nucleus, 231 226, 227, 259
RSNA. See Renal sympathetic nerve activity Sympathetic outflow Vascular remodeling
(RSNA) Ang II-evoked blood pressure, 111, 112–113, aortic aneurysm, 93
RVLM. See Rostral ventrolateral medulla 113f, 115f apoptosis, 89–90
(RVLM) baroreflex function, 111, 112f atherosclerosis, 92–93, 92f
complex and multifactorial process, 109 direct and indirect anti-inflammatory action, 90
components, 109
S neuronal electrophysiological characteristics,
heterodimerization, 90, 90f
Saralasin, 1 hypertension, 91–92
110 MAPK downregulation, 90
SARS. See Severe acquired respiratory NTS superoxide production, 111, 113f
syndrome (SARS) Marfan’s syndrome, 89
ontogeny, 109–110 mechanisms, 89–90
Scaffold protein CNK1, 105, 105f, 106 pathological conditions, 112
Severe acquired respiratory syndrome (SARS), NF-κB activity, 90
primary membrane receptors, 109 NO/cGMP pathway, 90
270 RSNA, 111, 112–113, 112f, 114f
Sex differences protein phosphatases, 90
sympathetic responses, 111, 112–113, 113f, small and larger recoil arteries, 89
arterial pressure, 126–127 115f
constrictor/vasodilator balance, 125–126, Vascular smooth muscle cells (VSMCs), 225, 243
therapeutic potential, 113f, 116f Vasodeleterious effects, 269–270
126f Sympathoexcitatory process, 109
downstream factors, 125 Vasodilation effects, 23, 49–50
Synthetic peptides ACE inhibitors, 198–199
estrogenic state, 125 β-amino acid-substituted angiotensin
function, 125 Ang-(1-7), 197, 198f
peptides, 144 antiproliferative action, 198
gene mapping, 125 CGP42112, 143
heart and vascular disease, 127–128 Mas-deficient mice, 197
LP2-3, 144 NO generation, 197, 198f
ischemic injury, 128 novokinin, 144–145
kidney, 127, 128f VSMCs, 198
[Y]6-AII, 144 Vasoprotective effects, 269–270
pain syndromes, 128
reproduction, 129 Vasorelaxation effects, 49, 52–53
stroke, 128 T
Spinal cord injury, 61 Tenascin C (TNC), 193 W
Stroke, 59–61, 67, 99, 128 TGF-β signaling, 214–215 Whole-cell patch-clamp techniques, 110
AT2R agonists, 152 Tissue inhibitor of metalloproteinase 3 Wistar-Kyoto (WKY) control, 84
cardiovascular disease, 99 (TIMP3), 105, 105f, 106
cerebral perfusion, 202 TNC. See Tenascin C (TNC)
cognitive function, 67 Transfersomes®, 276
Y
Yeast two-hybrid system, 105
DIZE, 203 Traumatic brain injury (TBI), 61
epidemiology, 201 Tumor fibrosis, 226–227
HSCs, 203–204 Type II diabetes mellitus, 152 Z
inflammation, 99 Tyrosine hydroxylase (TH), 232f, 235 Zinc finger (ZFN) technology, 161