биохимия атеросклероза

A

ABCA, see ATP-binding cassette (ABC), transporters

ABCA1, 3–6, 9, 12–14, 26, 39 alleles, 24, 40

degradation, 47 expression, 40, 45, 97 flippase activity, 46 internalization, 43 mutants, 44 pathway, 13

phosphorylation of, 45–47 ABCG, 95

ABCG1, 57, 92, 95–100, 219 ABCG4, 99

ABCG5, 11–12 hepatic, 57 ABCG8, 11–12 hepatic, 57

Abdominal aortic aneurysm, 176 Abdominal obesity, 286 Abetalipoproteinemia, 134 Aboriginals, 248

ACAT, see Acyl coenzyme A-cholesterol acyltransferase

Acellular lipid core, 457 Acetylation, 521 Acetylcholine, 437, 445, 481

Acetyl-CoA carboxylase (ACC), 221 N-Acetylcysteine, 262 Acetylhydrolase, 482

AcLDL, 75–76

Actinobacillus actinomycetemcomitans, 418–419

ACTION I, 267

ACTION II, 267

Activated protein C (APC), 153 Activating transcription factor 6 (ATF-6),

364–365

Acute coronary syndrome (ACS), 151, 156, 461

Acute lymphoblastic leukemia, 347

Acute myocardial infarction (AMI), 151, 158, 443, 455, 475; see also Myocardial infarction

and LDL size, 176

Acyl-coenzyme A-cholesterol acyltransferase (ACAT), 5, 9, 11, 92, 131–132

Acylglycerol-3-phosphate acyltransferase (AGPAT), 124, 126

1-Acylglycerol-3-phosphate, 124 Acylglycerols, 137 Acyltransferases, 137

Adaptor proteins, 213 Adenosine, 335 Adenosine deaminase, 335 Adenosine kinase, 335

S-Adenosylhomocysteine (SAH), 130, 334 S-Adenosylmethionine (SAM), 130, 329, 333 Adenylate cyclase, 5, 498

Adhesion

molecules, 439, 447 proteins, 288

Adipocytes, 213, 216, 256, 291 Adipokines, 216 Adiponectin, 215–217, 219 ADMA, see also Asymmetric

dimethylarginine

and vascular disease, 443–444 therapeutic reduction in transplant

arteriopathy, 446–447 Adrenaline, 498

Adult onset diabetes mellitus, 285 Advanced glycation end products (AGE),

257, 290, 294–296 atherosclerosis and hypertension,

305–319

554 Index

Advanced lipoxidation end products (ALE), 310 AGE(s), see also Advanced glycation end

products accumulation, 250, 267 adducts, 255

and endothelial dysfunction, 314–315 and oxidative stress, 311–313

and smooth muscle cells, 263–264 -carboxymethyl lysine (CML), 250 -epitopes, 251

formation, 247, 249, 257 inhibitors of, 266

due to insulin resistance, 309–310 -HDL, 255–256

-LDL, 256–259 autoantibodies, 255

proteins, 265 receptors, 262 structures, 251–252

“second generation”, 259 -RAGE pathway, 295

-RAGE signaling pathways, 293 AGE-modified lipoproteins, 253 AKT pathways, 214

Alagebrium, 296 Aldehydes, 247, 249

conjugates, 309–310 Aldose reductase, 289, 309 Allograft

coronary endothelial cells, 436 eNOS expression, 448

heart, 439 vasculature, 445

Alloxan, 287 ALT-711, 265, 268, 295

Alzheimer’s disease, 177, 329, 365, 386 Amadori products, 249, 294 “Amadori inhibitor”, 268

American Diabetes Association, 206 Aminoguanidine, 254, 265, 267–268, 295 Ammonia, 336

Amphetamines, 461 Amyloid β-peptide, 77, 259 Angina, 475, 479–480

pectoris, 495 recurrent, 424 unstable, 455–456 variant, 443

Angiotensin (AT1) receptors, 265 Angiotensin

I (AngI), 498

II (AngII), 150, 439, 458, 463, 498 Angiotensin-converting enzyme (ACE), 150,

158, 265, 498

Annexin V, 42 Antiapolipoprotein B, 535 Antiatherogenic phenotype, 508 Anticonvulsants, 346 Antigen-1, 484, 487

Antigen-4, 484 Antigen-presenting cells, 436

Antioxidant(s), 258, 310, 385, 519–527, 530–537

enzymes, 508

Antiphospholipid syndrome (APS), 153 Antithrombin III, 157

Aortic allografts, 444 Aortic lesions, 524

Aortic sinus atherosclerosis, 58 AP1, see Transcription factors ApoA

-I, see also Apolipoprotein, A-1 –ABCA1 interactions, 41–45 lipidation of, 43

lipid-free, 93, 99 Milano, 14, 94

-II, 26, 40, 44, 210 -IV, 40, 44, 98

ApoB, 24–30, 132, 137, 174, 207, 226, 531 /BATless mouse, 211

100, 123–124, 151, 170, 253, 478 B48, 124, 227

ApoB-containing lipoproteins, 33, 222–227 ApoC, 40, 98

-I, -II and -III, 44

ApoE, 8, 13, 26, 30–32, 40, 44, 57–58, 98, 264, 360, 397–398, 400, 460, 482

knockout mouse model, 287 null mice, 383, 419

ApoE/CBS-deficient double knockout mice, 362

Apolipoprotein, 3–7, 10, 44–45, 122, 463 A-1, 4–7, 24–32, 210, 256, 482

B, see ApoB B48, 227 CII, 193

E, see ApoE

E knockout (ApoE KO) mice, 58, 61, 158, 252

moiety, 535 mutations in, 24

Apoproteins, 25

Apoptosis, 54, 210, 253, 358, 387, 457–461 caspase-8-mediated, 81

ER stress-induced, 370 of VSMC, 440, 446

AR42J cells, 342 Arabinose, 253

Arachidonic acid (AA), 482, 498, 546–547 L-Arginine, 445, 497, 500

Arginine:glycine amidinotransferase (AGAT), 339

“Arginine paradox”, 441 Argpyrimidine, 310, 314 ARIC study, 417 Arrhythmias, 508 Arterial intima, 520

Arteriopathy, transplant, 435–448 Arteriosclerosis, 445, 495 Asbestos, 260

Aspirin, 546

Asymmetric dimethylarginine (ADMA), 369, 440–442, 445, 500

ATF6, 292

Atherogenesis, 70, 501, 537–538 infectious agents’ role in, 413–425

Atherogenic dyslipidemia, 205, 286 Atherogenic lipoprotein phenotype, 169 Atherogenic plaque, 495 Atherogenicity, 29

Atheroma, 259, 419, 443, 506, 524, 532 Atherosclerosis, 519

and LDL size, 176 aortic, 28–30 diet-induced, 59 LCAT in, 28

macrophage-specific influences on, 100 protection against, 54

Atherosclerotic aorta, 522–523 Atherosclerotic lesions, 416, 479–480,

523–524, 534, 536 formation and AGEs, 315–316

Atherosclerotic plaques, 456–457, 479, 523

Atherosclerotic vascular disease, 329 Atherothrombosis, 152 ATP-binding cassette (ABC)

transporter A1, see ABCA1 transporters, 5, 12, 40, 57, 92–95, 219; see

also ABCA1

Atrial natriuretic peptide, 439 Australian Aboriginals, 248 Autoantibodies, 29, 255 Autophosphorylation, 212 Azithromycin, 420, 424 Azuridine, 347

B

B cells, 404

B lymphocytes, 398–402

Bacteremia, 419

Bacteroides forsythus, 418

Index 555

BALBc mice, 287 Balloon angioplasty, 444 Bariatric surgery, 217 Beige mutation mice, 400 β-sheets, 259

Betaine, 335

Betaine homocysteine methyltransferase (BHMT), 335, 338, 342, 359

Big mitogen-activated protein kinase 1 (BMK1), 501

Bile acid(s), 4, 9, 11–12, 96, 131, 218 biosynthetic pathways, 188, 190 flux, 197

general structure of, 189 resins, 15

sequestrants, 347

Bile salt export pump (ABCB11), 9, 11 Biliary cholesterol, 12

pathway, 26 Bioactive lipids, 56, 72

Bio-breeding (BB) rat, 287 Blood

clotting, 545–547, 550 flow, 71, 416, 439, 445 glucose, 286

pressure, 311, 314, 546, 548 Bone marrow, 62, 101, 404

transplantation (BMT), 77, 100, 104, 403 Bovine arterial endothelial cells (BAEC), 82 Bowes human melanoma cells, 76

Brachial artery, 27 Brain infarction, 550

Bridging properties of HL, 10

Brown adipose tissue (BAT) knockout (KO) mouse, 211

C

Calcium channels, 311 influx, 314

Calnexin, 364 Calreticulin, 292, 364

cAMP response element-binding protein (CREB), 260, 366

Cancer, 346 Captopril, 158 Carbonyl(s), 266–267

stress, 247, 251, 258, 266 Carboxyethyl lysine (CEL), 255, 268,

310

Carboxymethyl lysine (CML), 250, 255, 259–260, 268, 310

Carcinoma, 222

Cardiac allografts, 447–448

556 Index

Cardiac transplant recipients, eNOS dysfunction in, 444–445

Cardiac transplantation, 446

Cardiovascular disease (CVD), 122, 130, 151, 248, 284, 519, 524

Cardiovascular disorders, hyperhomocysteinemia-induced, 380

Cardiovascular risk marker, 444

CARE, see Cholesterol and Recurrent Events study

Carnitine palmitoyl transferase (CPT) activity, 217

Carnitine, 334

Carotene, 258

β-Carotene, 317, 525, 527, 530, 533–534 Carotenoids, 530

Carotid artery

atherosclerosis, 158 disease, 175–176 stenosis, 250

intima, 158 plaques, 461 Caspases, 370, 457

Catalase, 508 Catechin, 482–483 Catecholamines, 460

Catechol-O-methyltransferase (COMT), 339

Cathepsins, 252, 459

Cationic amino acid transporter (CAT), 440–441

Caucasians, 345 Caveolin-1, 500, 505

Cb1 C deficiency, 343; see also Cobalamine CBS, see also Cystathionine β-synthase

deficiency, 387 mRNA, 341

C-C chemokine receptor (CCR2), 252, 380, 384, 386

CCAAT/enhancer-binding protein, 7 CD1d, 402

null mice, 403–404

CD36, 10, 70, 74, 77, 261, 288, 417 -TLR4 interactions, 78

CE, see also Cholesterol esters from HDL, 8

neutral, 25

selective uptake of, 13 Cell

death, 253, 292 debris, 477

signaling pathways, SR-BI in, 80–83 Cell-mediated cytotoxicity, 399

Cellular adhesion molecule (CAM) expression, 256, 260–263

Cellular lipid(s) export, 43 efflux of, 46

Ceramide, 56

Cerebral infarction, 548 Cerebral ischemia, 550

Cerebrotendinous xanthomatosis, 190 Cerebrovascular disease, 476, 495 Ceruloplasmin, 367

CETP see also Cholesterol ester transfer protein

inhibitors, 8, 14, 94 promoter, human, 7

c-fos, 263 Chaperones, 363–364

Chemoattractants, 520, 522 Chemokine(s), 362, 414, 436, 439,

447, 458, 525

expression, in vascular cells, 385–386 Chemotactic proteins, 72 Chenodeoxycholic acids, 188

Chlamydia pneumoniae (Cpn), 413–414, 417, 419–424, 458

Chlamydia trachomatis, 423 Chlamydial, 459

CHO cells, 80–81 -K1 cells, 81

3-[(3-Cholamidopropyl) dimethylammonio]-

1-propanesulfonate (CHAPS), 136 Cholesterol

7α-hydroxylase (cyp7a), 11, 187–188, 190; see also CYP7A1

absorption, 14–15, 253 acceptors, 13, 25 biosynthesis, 131, 382 catabolism, 186 crystals, 457, 477 dietary, 7

efflux, 4–7, 13, 40, 62, 80, 101, 256 ABC transporters and apoE in, 92 ABCA1-mediated, 45–46, 266 apolipoprotein-mediated, 43, 97 enhanced, 47

SR-BI-mediated, 56–57 in fibroblasts, 26

esters (CE), 9–11, 24, 92, 247, 457 transfer protein (CETP), 7, 14, 26, 32,

171, 463

esterificaton rate (CER), 32 free, 4, 8

HDL, 7, 10–11, 13–14 homeostasis, 10–12, 70, 92, 218

Cholesterol (Continued ) metabolism, 11–12 transport, 8, 11–12, 14

proteins, 12

Cholesterol and Recurrent Events study (CARE), 175, 208

Cholesteryl esters, 28, 71, 121, 257, 258 Cholestyramine, 193, 347

Cholic acids, 188 Choline, 340

kinase, 130 Chondrocytes, 82 Chromophores, 249

Chylomicron(s), 8, 56, 123, 210 remnants (CR), 227

Chymase, 458–459 Cirrhosis, 222 Citrulline, 441, 443, 497

c-Jun N-terminal protein kinases (JNK) , 75, 192, 214, 370

c-jun, 263

CLA-1 gene, SNP in, 10 CLAMPS, 60 Claudication, 307

CML, see also Carboxymethyl lysine epitopes, 251

-protein adduct, 252

CMV, in transplant endothelial dysfunction, 445–446

Coagulation, 151, 154, 504, 546, 550 Coantioxidants, 525, 533 Cob(I)alamin, 343, 345, 347 Cob(II)alamin, 345, 347 Cobalamine, 345, 347

Cobalamin metabolism, 343 Cocaine, 461

Coenzyme

A, 336

Q10, 310, 316 Colesevelam, 15 Colestipol, 347

Collagen, 251, 294, 311, 361, 459, 479, 486 Collaterals, 456, 461

Complete LCAT deficiency (CLD), 27 Coronary artery(ies)

endothelial vasodilator function of, 437 diseases (CAD), 27, 208, 330, 476, 527 atherosclerosis, 94, 175

culprit lesions, 455

endothelial vasodilator dysfunction, 444 heart disease (CHD), 23, 58, 168, 284, 413,

495, 519

heart disease and LDL size, 174–175 stenoses, 456

Index 557

syndrome, 480, 535–536 thrombi, 461 thrombosis, 455, 462

Corticosteroids, 7 COS-7 cells, 77

C-reactive protein, 418–419 Creatine, 329, 334, 336, 339

CREB, see cAMP response element-binding protein

C-type lectin-like domain (CLD), 83 CXCR-2, 252

Cyclic adenosine monophosphate (cAMP), 439, 442, 497–498

Cyclin A, 484 Cyclooxygenase (COX), 498

Cyclooxygenase-2 (COX-2), 481, 547 Cyclosporine, 443

A, 448

CYP7A1, 12

Cyp7a1 gene expression, 191–192 Cystathionine β-synthase (CBS), 335–338,

341, 343, 359, 383 Cystathionine γ-lyase (CGL), 335, 343 Cystathionine, 335–336 Cystathioninuria, 344

Cystatin-c, 459

Cysteine, 305, 318, 336, 366, 368 Cysteinylglycine, 366, 368

Cytidine diphosphocholine (CDP-choline), 130–131

Cytokines, 72, 253, 296, 362, 402, 458, 525 expression, 262

production, 502, 505 Cytomegalovirus (CMV), 413, 415–417,

435, 458 Cytosol, 45

Cytosolic free calcium and AGEs, 314

D

Deadly quartet, 208 Dendritic cells, 398, 402, 458 Deoxycoformycin, 347

3-Deoxyglucosone, 250, 267, 290 Dexamethasone, 341–342 Dgat-1 gene, 128

DGAT-1, overexpression of, 132 Dgat-2 gene, 128

Diabetes, 27, 34, 151, 175, 194, 221, 414, 458

type 1 (T1D), 253, 256, 263, 285

type 2 (T2D), 122, 205–208, 213, 265, 330 and LDL size, 177–178

Diabetes Atherosclerosis Intervention Study (DAIS), 209

558 Index

Diabetes Control and Complications Trial (DCCT), 248

Diabetes mellitus (DM), 32, 307, 341, 346, 441, 536

model systems, 286–288

and development of atherosclerosis, 284–296

Diabetes-induced atherosclerosis, 247 Diabetic atherosclerosis, animal models of,

264–266

Diabetic dyslipidemia, 208, 216, 254 Diabetic nephropathy, 158 Diacylglycerol (DAG), 46, 124, 293

Diacylglycerol acyltransferase (DGAT), 124, 127–128; see also DGAT-1

Diacylglycerol transacylase (DGTA), 128–129

Dialuric acid, 287 Dietary fats, 495, 504, 509 Dietary stearate, 546

Diethyl-p-nitrophenyl phosphate, 136 L-3,4-Dihydroxyphenylalanine (L-DOPA),

339, 347

Diisopropyl fluorophosphates, 136 Dimethylamine, 441, 443 Dimethylarginine dimethylaminohydrolase

(DDAH), 369, 441, 443, 446 Dimethylarginine dimethylaminohydrolase I

(DDAH-I) recipients, 447 N, N-Dimethylglycine, 335 Dimethylglycine, 335 Diphosphoglycerate, 309

DNA, 334 methylation, 338 oxidation of, 384 synthesis, 257, 480

Docosahexaenoic acid (DHA, 22:6), 507, 548

Dopamine, 339 Doppler flow wire, 437

Double knockout mice, 33 Down syndrome, 345 Doxycycline, 420 Drenomedullin, 439 Dysfunctional endothelium, 503

Dyslipidemia, 14, 32, 157, 177, 221, 268, 307, 435

E

Ectopia lentis, 359 Eicosanoids, 505–506, 508

Eicosapentaenoic acid (EPA), 482, 507 ELAM-1, 422

Elastase, 485

Elastin, 311, 459

Embolization, 504 Endocannabinoid system, 463 Endocarditis, 420

Endocytosis, 9, 152, 250, 257, 259, 261, 421 Endoplasmic reticulum (ER) stress, 291–293,

358, 363–366, 370, 387 Endosomal pathway, 8 Endothelial

cell protein C receptor (EPCR), 153 growth factor receptor (EGFR), 315 permeability, 477

thromboxane A2, 481 vasodilator dysfunction, 435

Endothelial dysfunction, 305, 358, 436, 487, 498–508, 536

and AGEs, 314–315

and atherosclerosis, 495–509, 495 Endothelial lipase (EL), 13–14, 94 Endothelial nitric oxide synthase (eNOS), 54,

61, 80, 314, 481 Endothelin, 439–440, 460, 498 Endothelin-1 (ET-1), 481

Endothelium-derived hyperpolarizing factor (EDHF), 498

Endotoxemia, 75 Endotoxin, 76

eNOS, see also Endothelial nitric oxide synthase

activation, 81

dysfunction in cardiac transplant recipients, 444–445

gene, 443

Enterohepatic circulatory pathway, 11 Enterohepatic metabolism of cholesterol,

11–12 Eotaxin, 458

Epicardial coronary vasoconstriction, 445 Epicardial vasodilatation, 437 EPIC-Norfolk study, 250

Epidermal growth factor (EGF), 459 Epinephrine, 334

24, 25-Epoxycholesterol, 96

ER stress response elements (ERSE), 365 ERK, see also Extracellular signal-regulated

kinase signaling, 225 1/2, 80 5, 501

Erythrocytes, 508

Erythromycin, 420 Erythrose, 253

E-selectin, 57, 156, 288, 361, 386, 478, 506 Estradiol, 56

Ethinyl estradiol, 337 Ethionine synthase, 342

Ethyl eicosapentaenoic acid (EPA), 546 Eukaryotic initiation factor-2α (eIF-2α),

292, 365

Extracellular matrix (ECM), 251, 288, 361, 459

Extracellular molecular targeting, 367–368 Extracellular signal-regulated kinase (ERK),

214, 220, 263 Ezetimibe, 15

F

F2-isoprostanes, 523 Factor V, 367 Factor Y, 387

Familial hypercholesterolemia (FH), 73, 177, 210

Farnesoid X receptor (FXR), 12, 186, 191, 194–197, 218

Farnesyl pyrophosphate, 157 FAT, 77

Fatty acids

n3-507–508, 545, 547, 549, 550 n6-, 551

Fatty acid synthase (FAS), 218, 221 Fatty acyl coenzyme A, 11

“Fatty streak”, 398, 414, 421, 479, 519, 521 Fc-γ receptors, 255

FED mutations, 27

Fenofibrate Intervention and Event Lowering

in Diabetes Study (FIELD), 209 Fenofibrate, 14

treatment, 209

FFA, see also Free fatty acid efflux, 217

flux, 205, 215–216, 223, 225, 227 metabolism, 211

oxidation, 217, 219 synthesis, 220–221

Fibrates, 14, 219 Fibrin, 368 Fibrinogen, 157, 505

Fibrinolysis, 151, 154, 157, 546 Fibrinolytic activity, 461

Fibroblasts, 5, 26, 42, 97, 256, 500, 522 Fibroblast growth factor (FGF), 503 Fibrofatty plaques, 436

Fibronectin, 367–368 Fibrosis, 222, 414 “Fibrotic plaque”, 414 Fibrous cap, 456, 459 Fibrous plaques, 421 Fish-eye disease (FED), 27

Index 559

Flavoenzyme, 335 Flavonoids, 483, 531, 534

Flow-mediated dilatation (FMD), 27 Flow-mediated vasodilation (FMVD), 441 Fluorescence photobleaching technique, 41 Fluorophores, 249

Foam cell, 72, 247, 358, 398, 457, 477, 501, 534 death, 288

formation, 254, 256–259 Folate, 337, 347, 381, 530

metabolism, 346 Folic acid, 329, 359, 386 Foxa1, 194–195

Foxo1, 192

Framingham Heart Study, 24, 331, 344 Frank rupture, 460

Free cholesterol (FC), 11, 24–25, 92, 457 bidirectional flux of, 95

Free fatty acid (FFA), 207, 210, 212, 218 FXR, see also Farnesoid X receptor

target genes, 197 farnesoid X receptor, 3

Fyn, 77

G

α-Galactosylceramide, 401 α-GalCer, 402–403 Galectin-3, 262

Gallbladder disease, 122, 286 Gallstone, 190

Gangrene, 307

Gemfibrozil, 14

Genetic polymorphisms, 329 Geranyl pyrophosphate, 157

Geranylgeranyl pyrophosphate (GGPP), 97 Gingivitis, 418

Glibenclamide, 42 Glitazones, 209 Glomerulopathy, 262

Glu298Asp, 443 Glucagons, 341, 343 Glucocorticoid(s), 341, 343

receptor, 194–195 Gluconeogenesis, 33, 197, 205 Glucose, 152, 247, 249, 253, 309

biosynthetic pathway, 194 homeostasis, 210, 219 intolerance, 207 metabolism, 305, 308 tolerance, impaired, 210

transporter 4 (GLUT4), 214, 285, 291 Glucose-6-phosphatase (G6Pase), 194 β-Glucuronidase, 485

GLUT1 transporter, 259

560 Index

GLUT2 transporter, 287 Glutamine:fructose-6 phosphate

amidotransferase (GFAT), 290 Glutathione, 310–311, 336, 366, 368, 483 Glutathione peroxidase (GPx), 310–311

expression, 363

Glutathione peroxidase (GPx-1) activity, 369 Glutathione reductase, 252, 311

Glycated hemoglobin (HbA1c), 248 Glycation, 152, 155, 249

Glycemia, 217, 264–265 Glyceraldehyde, 253

-3-phosphate (G3P), 309 Glyceraldehyde-3-phosphate dehydrogenase

(GAPDH), 252, 309 Glycerol, 134, 222

-3-phosphate pathway, 125 Glycerol-3-phosphate acyltransferase (GPAT)

125–126, 128

Glycine N-methyltransferase (GNMT), 334 Glycine, 335

Glycogen synthesis, 213, 222 Glycolaldehyde, 249–250, 253, 257–258, 261

-pyridine, 310 Glycolytic pathway, 309 β-Glycoprotein, 458 Glycosphingolipid, 402

O-linked Glycosylation, 291 Glycoxidation, 247, 249 Glyoxal, 267, 309

GNMT, 338, 342 Goto Kakizaki rat, 287 Gout, 208

GPIV, 77

G-proteins, 75–76, 158 Graft atherosclerosis, 444 Graft ischemia, 448 Granzyme, 399

A promoter, 400 Grb-2-SOS complex, 213

Growth arrestand DNA damage-inducible gene 153 (GADD153), 292, 365

Growth hormone, 342 GRP78, 292, 364–365 GRP94, 292, 364–365 GTPases, 260 GTP-cyclohydrolase I, 61

Guanidinoacetate methyltransferase, 339 Guanidinoacetic acid (GAA), 339 Guanylate cyclase, 497

H

H4IIE cells, 341–342

Haemopoetic atherogenesis, 362

HbA1c, 250

HCAECs, see Human, coronary artery endothelial cells

HDL, see also High-density lipoproteins apolipoproteins, 40

apoproteins, 40, 46 biogenesis of, 93, 96 cholesterol, 226 deficiency, 24, 26, 31 nascent pre-β-, 7, 13, 96 receptor, 54

spherical, 4, 7, 13 syndromes, low, 33 HDL-SR-BI ligation, 81

Heart attack, 121

disease, 307 failure, 441

transplantation, 435 HEART study, 158

Heat shock proteins (HSP), 156–157, 458–459

60 (hsp60), 422–423 HEK 293 cells, 99–100 HeLa cells, 80, 385

Helicobacter pylori (Hpy), 413, 417–418 Helix-loop-helix

-leucine zipper transcription factors, 220

zipper proteins, 387 Hematoma, 399 Hematopoietic stem cells, 100 Heme oxygenase-1 (HO-1), 363 Heme proteins, 439 Hemodialysis, 533 Hemoglobin (HbA1c), 254

glycated (HbA1c), 295 Hemorrhage, 477

Hemorrhagic stroke, 545–546, 548–551 Hemostasis, 486, 496, 546

Heparans, 499 Heparin, 156, 368

sulfate proteoglycans, 8 Hepatic lipase, 8, 171

Hepatic lipid metabolism, 387–388 Hepatic steatosis, 221, 286, 359 Hepatic VLDL

assembly, 121 overproduction, 223 production, 222 TG production, 223

Hepatocellular necrosis, 221

Hepatocyte(s), 124, 223, 261, 292, 339, 382, 531 nuclear factor-4 (HNF-4), 3; see also

HNF1; HNF-3α and -4α

nuclear factor-4α (HNF-4α), 12, 194–195 Hepatoma

cell lines, 132 H4IIE cells, 342

HepG2 cells, 10, 132, 135, 223, 341 Herp, 365

Herpes simplex virus type 2, 415 Herpesviruses (HPV), 413, 415–417, 445–446 Hexosamine pathway, 249, 290–292

Hcy

expression, 385–386

metabolism, 329, 333, 336–338, 381–382 HHcy

-induced atherogenesis, animal models of, 360–362

-induced CVD, molecular and biochemical mechanisms of, 380

High-density lipoproteins (HDL), 5, 11, 14, 39, 475, 526

cholesterol (HDL-C), 23–24, 27, 29, 40 High-mobility group protein B1 (HMGB1),

259

High-plasma homocysteine, 414 High-sensitivity C-reactive protein (hs-CRP),

482 HIV, 415 HL, 8, 13–14

-60 cells, 370

HMG-CoA, see Hydroxy-3-methylglutaryl coenzyme A

HMG-CoA reductase, 10, 157, 209–210, 366, 387

HNF 1, 192

-4, 1, 192

-3α and -4α, 194–195 Holoprotein, 96 Homeostasis, 95, 314 L-35S-Homocysteine, 368

Homocysteine (Hcy), 293, 362, 530 hepatic lipid metabolism and, 387–388 plasma forms of, 331–333

kidney injury and, 388 thiolactonase, 333 thiolactone, 332, 367, 370

Homocysteinemia, 333 Homocysteinuria, 329, 343–344, 347, 359 Homocysteinylated-factor V (Va), 368 Hordaland homocysteine study, 337, 345 Hordaland study, 387

Hormone(s), 329, 496

sensitive lipase (HSL), 135, 215 HTG, see Hypertriglyceridemia

Index 561

Human

apoB transgenic mouse, 211 CMV, 445

coronary artery endothelial cells (HCAEC), 81–82

factor V, 368

hepatoma cell (HepG2), 387 line, 341

monocyte-derived macrophages (HMDM), 257

umbilical endothelial cells, 484

umbilical vein endothelial cells (HUVEC), 481

Hydrocortisone, 342–343 Hydrogen peroxide, 310

Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), 3, 150, 476

α-Hydroxyaldehydes, 266 Hydroxycholesterols, 96

7α-, 187–188 HyperapoB, 227

Hyperbetalipoproteinemia, 170 Hypercholesterolemia, 71, 131, 150, 210, 441,

476, 487 familial, 521

Hypercoagulability, 248

Hyperglycemia, 153, 207, 210, 248–254, 267, 443

chronic, 285, 295 streptozotocin-induced, 289

Hyperhomocysteinemia (HHcy), 329–332, 337, 441, 443

atherosclerosis and, 362 endothelial function and, 383

genetic and nutritional factors, 359–360 nonphysiological causes of, 343–346 role in atherosclerosis, 358

Hyperinsulinemia, 205, 210–211, 218, 221, 287 Hyperlipidemia, 28, 122, 170, 208, 287,

414, 443 Hyperphagia, 211 Hyperplasia, 210

Hypertension, 71, 175, 207, 222, 296, 414, 443

atherosclerosis, and AGE products, 305–319

risk factors, 306 Hyperthemia, 157

Hypertriglyceridemia (HTG), 8, 27, 32–33 153, 171, 196, 210, 227

Hypoalphalipoproteinemia, 170 Hypochloride, 152 Hypochlorous acid (HOCl), 310 Hypoxia, 343, 498

562 Index

I

IκB kinases, 385

ICAM, see Intercellular adhesion molecule IHD, see Ischemic heart disease

IKK

-α, 385 -β, 385

Immune system in atherosclerosis, 397–405 Immunogenicity, 254 Immunoinflammatory disease, 463 Immunosuppression, 443 Immunosuppressive agents, 435, 448 Inducible nitric oxide synthase (iNOS), 384,

444, 481 Infertility, 209, 286

Inflammation, 71, 150, 221, 305, 362, 419, 519

Inflammatory cells, 458–459, 461 Inflammatory cytokines, 447 Inflammatory diseases, 156 Inflammatory markers, 81, 216–217, 422 Inflammatory pathways, 80, 293 Innominate artery, 460

iNOS knockout mice, 444 INSIG-1, 220

Insulin, 10, 341, 343, 531

-dependent diabetes mellitus (IDDM), 285 dyslipidemia, 221–222

pathway, 213

receptor (IR) signaling pathway, 211 resistance, 28, 32, 206, 286, 435, 458 -resistant states, 205

signaling, 220–221

substrate (IRS), 213–214, 219 syndrome, 177, 208, 217, 308

Integrin(s), 502 β2, 288, 485

Intercellular adhesion molecule (ICAM), 288 -1 (ICAM-1), 293, 417, 422, 478, 502

Interferon (IFN-γ), 7, 97, 288, 399–405, 458, 502

Interleukin(s), 502 -α, 10

-1 (IL-1), 97, 255, 422, 478 -2 (IL-2), 403

-4 (IL-4), 402–403

-6 (IL-6), 76, 263, 417, 419, 422 -8, 80, 362, 414, 422, 458

receptor, 252

-10 (IL-10), 403, 458 -12 (IL-12), 402, 405 -18 (IL-18), 405

Intermediate-density lipoprotein (IDL), 30, 33, 170

International Diabetes Federation (IDF), 206

Intima, 71–72, 156, 288 Intimal hyperplasia, 436

Intima-medial thickness (IMT), 27, 178, 443 Intracellular adhesion molecule-1 (ICAM-1),

156, 263 Intracellular mediators, 157

Intracellular molecular targeting, 368–370 Intracerebral hemorrhage, 550 Intravascular thrombosis, 477

IRE(s), 226

-1, 292, 364–366 signaling, 370

Ischemia-reperfusion, 435–436 Ischemic heart disease (IHD), 151, 158,

507

Ischemic stroke, 413, 415, 418, 545, 548–551, 546

Ischemic sudden death, 455–456 Isoniazid, 347

Isoprostanes, 547

J

Jα18 null mice, 404 JAK/STAT pathway, 221, 260

Janus kinase 2 (JAK2), 3, 5–6, 46, 214 JCR: LA corpulent rat, 210

JTT-705, 14

Juvenile diabetes, 285

K

Kennedy pathway, 340 α-Ketobutyrate, 336 Kidney

disease, 307 failure, 316 injury, 386, 388

KK mouse, 287 Krebs’ cycle, 336 Kupffer cells, 137

L

Lactate dehydrogenase (LDH), 252 Laminin, 294

Lauric acid, 504

LCAT, see also Lecithin cholesterol acyltransferase

activity, 26, 29, 57 in atherosclerosis, 28 deficiency, 23, 30–34 gene, 24, 26, 28–31

knockout mice, 23, 30, 34 mutations, 27, 31