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Trends indicate that the metabolic syndrome will become the leading risk factor for heart disease. Now more than ever you need an all-in-one reference that provides the tools and practical advice you need to: Identify at-risk patients Explain individual contributing factors Aid in patient education and motivation Direct comprehensive care and Choose the most appropriate interventions
Comprehensively revised to reflect leading-edge research and now organized to facilitate easy access to essential information and clinically-relevant guidance, Metabolic Syndrome and Cardiovascular Disease, 2e…mehr
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Trends indicate that the metabolic syndrome will become the leading risk factor for heart disease. Now more than ever you need an all-in-one reference that provides the tools and practical advice you need to:
Identify at-risk patients
Explain individual contributing factors
Aid in patient education and motivation
Direct comprehensive care and
Choose the most appropriate interventions
Comprehensively revised to reflect leading-edge research and now organized to facilitate easy access to essential information and clinically-relevant guidance, Metabolic Syndrome and Cardiovascular Disease, 2e offers this and more. Not only will you receive a solid understanding of the pathophysiology underlying the metabolic syndrome and cardiovascular disease but also the rationale for today's most effective treatments.
What's new?
Filled with timely new content, this updated edition covers:
New discoveries that have changed our understanding of the pathogenesis and interrelationship of metabolic syndrome, cardiovascular disease (CHD), and type 2 diabetes mellitus (DM)
The relevance of mitochondria and telomeres
Sleep and its impact on cardiometabolic health
The pivotal interplay between insulin and forkhead transcriptionfactors
Calorie restriction research
Bariatric surgery experiences and outcomes
In addition, each chapter includes essential information on comorbidities, interventions, and pharmacotherapeutic options - an exclusive feature found only in the second edition!
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Identify at-risk patients
Explain individual contributing factors
Aid in patient education and motivation
Direct comprehensive care and
Choose the most appropriate interventions
Comprehensively revised to reflect leading-edge research and now organized to facilitate easy access to essential information and clinically-relevant guidance, Metabolic Syndrome and Cardiovascular Disease, 2e offers this and more. Not only will you receive a solid understanding of the pathophysiology underlying the metabolic syndrome and cardiovascular disease but also the rationale for today's most effective treatments.
What's new?
Filled with timely new content, this updated edition covers:
New discoveries that have changed our understanding of the pathogenesis and interrelationship of metabolic syndrome, cardiovascular disease (CHD), and type 2 diabetes mellitus (DM)
The relevance of mitochondria and telomeres
Sleep and its impact on cardiometabolic health
The pivotal interplay between insulin and forkhead transcriptionfactors
Calorie restriction research
Bariatric surgery experiences and outcomes
In addition, each chapter includes essential information on comorbidities, interventions, and pharmacotherapeutic options - an exclusive feature found only in the second edition!
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Verlag: Blackwell Publishers / Wiley-Blackwell
- Artikelnr. des Verlages: 1A405195750
- 2. Aufl.
- Seitenzahl: 512
- Erscheinungstermin: 1. Oktober 2012
- Englisch
- Abmessung: 292mm x 228mm x 33mm
- Gewicht: 1480g
- ISBN-13: 9781405195751
- ISBN-10: 1405195754
- Artikelnr.: 36027119
- Verlag: Blackwell Publishers / Wiley-Blackwell
- Artikelnr. des Verlages: 1A405195750
- 2. Aufl.
- Seitenzahl: 512
- Erscheinungstermin: 1. Oktober 2012
- Englisch
- Abmessung: 292mm x 228mm x 33mm
- Gewicht: 1480g
- ISBN-13: 9781405195751
- ISBN-10: 1405195754
- Artikelnr.: 36027119
T. Barry Levine, MD, FACC, is Chief Medical Officer, A.B.L.E. Medical Consulting. He is Professor of Medicine at Drexel University College of Medicine in Philadelphia, PA. Dr. Levine is a Fellow of the American College of Cardiology, a member of the Scientific Advisory Board of the International Academy of Cardiology, and a board member of the Tracleer International Scientific Advisory Board. In addition, he is a member of the American Federation for Clinical Research, the American Heart Association, the International Society for Heart and Lung Transplantation, the American College of Chest Physicians, and the Heart Failure Society of America. Dr. Levine has been recognized by his peers in "Best Doctors in America" and "Top Docs in Pittsburgh". Dr. Levine has participated in numerous clinical trials, authored many articles (138), and created a variety of media presentations on heart failure, hypertension, dyslipidemia, and metabolic syndrome. He along with Dr. Arlene B. Levine has written "A Patient's Guide to Heart Failure" and has authored a textbook, "Metabolic Syndrome and Cardiovascular Disease". Arlene Bradley Levine, MD, FACC, is CEO, A.B.L.E. Medical Consulting. She is Assistant Professor of Medicine at Michigan State University and? is board-certified in Internal Medicine and Cardiovascular Disease. Dr. Levine is a Fellow of the American College of Cardiology. She is a member of the American Heart Association, the International Society for Heart and Lung Transplantation, the American College of Chest Physicians, and the Heart Failure Society of America. Dr. Levine has authored 45 articles, and has been recognized by her peers in "Best Doctors in America" and "Top Docs in Pittsburgh".
Preface viii
List of Abbreviations ix
1 The Metabolic Syndrome: A Relevant Concept? 1
2 Mitochondria 3
Background 3
Cellular respiration 6
Modulation of mitochondrial metabolic activity 9
Factors that affect mitochondrial number and activity 10
Peroxisome proliferator-activated receptor gamma coactivator-1 11
Mitochondrial production of prooxidant species 12
Mitochondria and nitric oxide 15
Mitochondrial calcium homeostasis 17
The mitochondrial permeability transition 18
Apoptosis 22
Causes for mitochondrial dysfunction 22
Implications of mitochondrial dysfunction 27
Mitochondrial dysfunction and cardiovascular disease 27
Mitochondrial dysfunction and metabolic disease 29
Conclusion 32
Bibliography 34
3 Telomeres 40
Telomere structure 40
Telomere function 41
Telomere shortening 41
Telomere dysfunction 42
Physiologic age 42
Gender differences 43
Telomerase 43
Cell senescence and apoptosis 46
Telomeres in aging 49
Risk factors for cardiometabolic disease 51
Telomeres senescence and chronic disease 54
Cardiovascular disease 54
Insulin resistance and type 2 DM 57
Conclusion 58
Bibliography 60
4 The FoxO Transcription Factors and Sirtuins 64
Forkhead transcription factors 64
Functions of FoxO 68
Cardiovascular forkhead effects 70
Metabolic forkhead effects 72
Histone acetylation and deacetylation 75
Sirtuin deacetylases 76
Sirtuin regulation 78
Antiinflammatory cardiovascular and myocyte sirtuin effects 80
Sirtuin effects on metabolism 81
Sirtuins and cell longevity 83
Forkhead deregulation and insulin resistance 85
Paradoxical effect of nutrition versus stress on cell death suppression
87
Conclusion 89
Bibliography 90
5 Insulin and Insulin-Like Growth Factor 96
Anabolism and catabolism 96
Control of plasma glucose 96
Insulin 97
Insulin receptor location 98
Metabolic insulin signaling 101
Insulin-mediated glucose uptake 103
Nutrient storage and metabolism 104
Vascular and antiinflammatory effects 106
Mitogenic action 107
Insulin-like growth factor 108
Insulin and IGF impact on cell longevity 111
Amylin 113
Glucagon 113
Conclusion 113
Bibliography 114
6 Oxidative Stress 120
Free radicals 120
Oxidases 120
Sources for free radicals 123
Endogenous antioxidants 124
Physiologic functions of oxidative stress 126
Mechanisms of oxidative damage 127
Cellular stress-sensitive pathways 127
Cellular targets of oxidative stress 128
Oxidative stress-related diseases 129
Endothelial dysfunction with oxidative stress 129
Cardiovascular disease 130
Insulin resistance and type 2 DM 131
Conclusion 133
Bibliography 134
7 Mental Stress 139
Stress responses 139
Central stress pathways 139
Peripheral stress pathways 140
Fight-flight-fright responses to acute stress 142
Sequelae of sustained passive stress 142
Inflammatory effects of stress pathways 143
Vascular and lipoprotein effects of
stress pathways 143
Stress impact on body weight 146
Metabolic effects of stress pathways 146
Depression and other mood disturbances 149
Conclusion 152
Bibliography 153
8 Sleep 159
Stages of sleep 159
Cardiovascular parameters during normal sleep 160
Function of sleep 161
Sleep duration 164
Circadian rhythm 165
Examples of circadian regulation 166
Neurohormonal modulation of wakefulness 168
Neurohormonal modulation of sleep 170
Sleep-arousal transitions 172
Sleep deficit 174
Pathophysiologic effects of sleep debt 175
Sleep debt and risk of cardiometabolic disorder 177
Sleep disorders 179
Conclusion 182
Bibliography 183
9 Inflammation 192
Immune responses 192
Selected participants in the inflammatory response 193
C-reactive protein 198
The renin-angiotensin-aldosterone system and inflammation 199
Inflammation and chronic diseases 202
Inflammation endothelial and vascular dysfunction 202
Inflammation and atherosclerosis 205
Acute inflammation carbohydrate metabolism and dyslipidemia 210
Chronic inflammation and the metabolic syndrome 213
Causes for systemic inflammation 215
Conclusion 218
Bibliography 219
10 Adipose Tissue and Overweight 228
Energy storage 228
Diverse fat depots 230
Adipose tissue as immune organ 234
Adipose tissue as endocrine organ 236
Adipokines with beneficial cardiometabolic effect 237
Adipokines with detrimental cardiometabolic effect 244
Obesity comorbidities and cardiovascular disease 250
Obesity insulin resistance and diabetes 252
Conclusion 254
Bibliography 255
11 Weight Loss and Diet 266
Homeostatic responses to weight gain and weight loss 266
Adipose weight loss effects 267
Antiinflammatory vasculoprotective and metabolic effects of weight loss
267
Dietary intervention for weight loss 269
Calorie restriction 270
Surgical intervention 277
Diet 279
Exercise as adjunct to weight loss 289
Conclusion 289
Bibliography 291
12 Skeletal Muscle and Exercise 303
Myocyte structure and function 303
Metabolic adaptations in skeletal muscle 305
Energy sensors 311
Skeletal muscle in inflammation 317
Skeletal muscle in insulin resistance 318
Exercise effect on inflammation and oxidative stress 320
Exercise effect on metabolism in obesity 322
Exercise effect and cardiovascular health 322
Exercise and insulin resistance 325
Exercise and mortality 328
Exercise recommendation 331
Conclusion 332
Bibliography 334
13 Lipids Atherogenic Dyslipidemia and Therapy 347
Apolipoproteins 347
Lipoproteins 347
Apo A-containing lipoproteins 348
Apo B-containing lipoproteins 355
Apolipoproteins C D and E 360
The triglyceride lipase family 360
The normal metabolism of free fatty acids 363
Inflammation and hepatic insulin resistance 365
Atherogenic dyslipidemia in insulin resistance 369
Lipid-lowering therapy 372
The HMG CoA reductase inhibitors 374
Nicotinic acid 387
The fibric acid derivatives 388
Bile acid sequestrants 391
Ezetimibe 391
CETP inhibition 391
Conclusion 392
Bibliography 393
14 The Endothelium Cardiovascular Disease and Therapy 409
Endothelial function 409
Nitric oxide synthase and eNOS 409
Endothelial NO synthesis 410
Specific enhancers of NO synthesis 413
Functions of nitric oxide 415
Shear stress and vascular function 418
Mechanisms of endothelial dysfunction 420
Insulin insulin resistance and endothelial dysfunction 424
Implications of endothelial dysfunction 428
Assessment of endothelial function 430
Hypertension 432
Cardiomyopathy 434
Coronary and peripheral vascular disease 440
Pharmacologic antagonism of the renin-angiotensin-aldosterone system and
endothelin-1 443
Beta-adrenergic blockade 448
Phosphodiesterase-5 inhibitors 449
Conclusion 450
Bibliography 451
15 Insulin Resistance Metabolic Syndrome and Therapy 468
Diagnostic criteria for the metabolic syndrome 468
Prevalence of the metabolic syndrome 470
Insulin resistance 470
Causes of insulin resistance 474
Pathways toward insulin resistance 476
Pharmacologic therapy to improve insulin sensitivity 480
Conclusion 483
Bibliography 484
Index 491
List of Abbreviations ix
1 The Metabolic Syndrome: A Relevant Concept? 1
2 Mitochondria 3
Background 3
Cellular respiration 6
Modulation of mitochondrial metabolic activity 9
Factors that affect mitochondrial number and activity 10
Peroxisome proliferator-activated receptor gamma coactivator-1 11
Mitochondrial production of prooxidant species 12
Mitochondria and nitric oxide 15
Mitochondrial calcium homeostasis 17
The mitochondrial permeability transition 18
Apoptosis 22
Causes for mitochondrial dysfunction 22
Implications of mitochondrial dysfunction 27
Mitochondrial dysfunction and cardiovascular disease 27
Mitochondrial dysfunction and metabolic disease 29
Conclusion 32
Bibliography 34
3 Telomeres 40
Telomere structure 40
Telomere function 41
Telomere shortening 41
Telomere dysfunction 42
Physiologic age 42
Gender differences 43
Telomerase 43
Cell senescence and apoptosis 46
Telomeres in aging 49
Risk factors for cardiometabolic disease 51
Telomeres senescence and chronic disease 54
Cardiovascular disease 54
Insulin resistance and type 2 DM 57
Conclusion 58
Bibliography 60
4 The FoxO Transcription Factors and Sirtuins 64
Forkhead transcription factors 64
Functions of FoxO 68
Cardiovascular forkhead effects 70
Metabolic forkhead effects 72
Histone acetylation and deacetylation 75
Sirtuin deacetylases 76
Sirtuin regulation 78
Antiinflammatory cardiovascular and myocyte sirtuin effects 80
Sirtuin effects on metabolism 81
Sirtuins and cell longevity 83
Forkhead deregulation and insulin resistance 85
Paradoxical effect of nutrition versus stress on cell death suppression
87
Conclusion 89
Bibliography 90
5 Insulin and Insulin-Like Growth Factor 96
Anabolism and catabolism 96
Control of plasma glucose 96
Insulin 97
Insulin receptor location 98
Metabolic insulin signaling 101
Insulin-mediated glucose uptake 103
Nutrient storage and metabolism 104
Vascular and antiinflammatory effects 106
Mitogenic action 107
Insulin-like growth factor 108
Insulin and IGF impact on cell longevity 111
Amylin 113
Glucagon 113
Conclusion 113
Bibliography 114
6 Oxidative Stress 120
Free radicals 120
Oxidases 120
Sources for free radicals 123
Endogenous antioxidants 124
Physiologic functions of oxidative stress 126
Mechanisms of oxidative damage 127
Cellular stress-sensitive pathways 127
Cellular targets of oxidative stress 128
Oxidative stress-related diseases 129
Endothelial dysfunction with oxidative stress 129
Cardiovascular disease 130
Insulin resistance and type 2 DM 131
Conclusion 133
Bibliography 134
7 Mental Stress 139
Stress responses 139
Central stress pathways 139
Peripheral stress pathways 140
Fight-flight-fright responses to acute stress 142
Sequelae of sustained passive stress 142
Inflammatory effects of stress pathways 143
Vascular and lipoprotein effects of
stress pathways 143
Stress impact on body weight 146
Metabolic effects of stress pathways 146
Depression and other mood disturbances 149
Conclusion 152
Bibliography 153
8 Sleep 159
Stages of sleep 159
Cardiovascular parameters during normal sleep 160
Function of sleep 161
Sleep duration 164
Circadian rhythm 165
Examples of circadian regulation 166
Neurohormonal modulation of wakefulness 168
Neurohormonal modulation of sleep 170
Sleep-arousal transitions 172
Sleep deficit 174
Pathophysiologic effects of sleep debt 175
Sleep debt and risk of cardiometabolic disorder 177
Sleep disorders 179
Conclusion 182
Bibliography 183
9 Inflammation 192
Immune responses 192
Selected participants in the inflammatory response 193
C-reactive protein 198
The renin-angiotensin-aldosterone system and inflammation 199
Inflammation and chronic diseases 202
Inflammation endothelial and vascular dysfunction 202
Inflammation and atherosclerosis 205
Acute inflammation carbohydrate metabolism and dyslipidemia 210
Chronic inflammation and the metabolic syndrome 213
Causes for systemic inflammation 215
Conclusion 218
Bibliography 219
10 Adipose Tissue and Overweight 228
Energy storage 228
Diverse fat depots 230
Adipose tissue as immune organ 234
Adipose tissue as endocrine organ 236
Adipokines with beneficial cardiometabolic effect 237
Adipokines with detrimental cardiometabolic effect 244
Obesity comorbidities and cardiovascular disease 250
Obesity insulin resistance and diabetes 252
Conclusion 254
Bibliography 255
11 Weight Loss and Diet 266
Homeostatic responses to weight gain and weight loss 266
Adipose weight loss effects 267
Antiinflammatory vasculoprotective and metabolic effects of weight loss
267
Dietary intervention for weight loss 269
Calorie restriction 270
Surgical intervention 277
Diet 279
Exercise as adjunct to weight loss 289
Conclusion 289
Bibliography 291
12 Skeletal Muscle and Exercise 303
Myocyte structure and function 303
Metabolic adaptations in skeletal muscle 305
Energy sensors 311
Skeletal muscle in inflammation 317
Skeletal muscle in insulin resistance 318
Exercise effect on inflammation and oxidative stress 320
Exercise effect on metabolism in obesity 322
Exercise effect and cardiovascular health 322
Exercise and insulin resistance 325
Exercise and mortality 328
Exercise recommendation 331
Conclusion 332
Bibliography 334
13 Lipids Atherogenic Dyslipidemia and Therapy 347
Apolipoproteins 347
Lipoproteins 347
Apo A-containing lipoproteins 348
Apo B-containing lipoproteins 355
Apolipoproteins C D and E 360
The triglyceride lipase family 360
The normal metabolism of free fatty acids 363
Inflammation and hepatic insulin resistance 365
Atherogenic dyslipidemia in insulin resistance 369
Lipid-lowering therapy 372
The HMG CoA reductase inhibitors 374
Nicotinic acid 387
The fibric acid derivatives 388
Bile acid sequestrants 391
Ezetimibe 391
CETP inhibition 391
Conclusion 392
Bibliography 393
14 The Endothelium Cardiovascular Disease and Therapy 409
Endothelial function 409
Nitric oxide synthase and eNOS 409
Endothelial NO synthesis 410
Specific enhancers of NO synthesis 413
Functions of nitric oxide 415
Shear stress and vascular function 418
Mechanisms of endothelial dysfunction 420
Insulin insulin resistance and endothelial dysfunction 424
Implications of endothelial dysfunction 428
Assessment of endothelial function 430
Hypertension 432
Cardiomyopathy 434
Coronary and peripheral vascular disease 440
Pharmacologic antagonism of the renin-angiotensin-aldosterone system and
endothelin-1 443
Beta-adrenergic blockade 448
Phosphodiesterase-5 inhibitors 449
Conclusion 450
Bibliography 451
15 Insulin Resistance Metabolic Syndrome and Therapy 468
Diagnostic criteria for the metabolic syndrome 468
Prevalence of the metabolic syndrome 470
Insulin resistance 470
Causes of insulin resistance 474
Pathways toward insulin resistance 476
Pharmacologic therapy to improve insulin sensitivity 480
Conclusion 483
Bibliography 484
Index 491
Preface viii
List of Abbreviations ix
1 The Metabolic Syndrome: A Relevant Concept? 1
2 Mitochondria 3
Background 3
Cellular respiration 6
Modulation of mitochondrial metabolic activity 9
Factors that affect mitochondrial number and activity 10
Peroxisome proliferator-activated receptor gamma coactivator-1 11
Mitochondrial production of prooxidant species 12
Mitochondria and nitric oxide 15
Mitochondrial calcium homeostasis 17
The mitochondrial permeability transition 18
Apoptosis 22
Causes for mitochondrial dysfunction 22
Implications of mitochondrial dysfunction 27
Mitochondrial dysfunction and cardiovascular disease 27
Mitochondrial dysfunction and metabolic disease 29
Conclusion 32
Bibliography 34
3 Telomeres 40
Telomere structure 40
Telomere function 41
Telomere shortening 41
Telomere dysfunction 42
Physiologic age 42
Gender differences 43
Telomerase 43
Cell senescence and apoptosis 46
Telomeres in aging 49
Risk factors for cardiometabolic disease 51
Telomeres senescence and chronic disease 54
Cardiovascular disease 54
Insulin resistance and type 2 DM 57
Conclusion 58
Bibliography 60
4 The FoxO Transcription Factors and Sirtuins 64
Forkhead transcription factors 64
Functions of FoxO 68
Cardiovascular forkhead effects 70
Metabolic forkhead effects 72
Histone acetylation and deacetylation 75
Sirtuin deacetylases 76
Sirtuin regulation 78
Antiinflammatory cardiovascular and myocyte sirtuin effects 80
Sirtuin effects on metabolism 81
Sirtuins and cell longevity 83
Forkhead deregulation and insulin resistance 85
Paradoxical effect of nutrition versus stress on cell death suppression
87
Conclusion 89
Bibliography 90
5 Insulin and Insulin-Like Growth Factor 96
Anabolism and catabolism 96
Control of plasma glucose 96
Insulin 97
Insulin receptor location 98
Metabolic insulin signaling 101
Insulin-mediated glucose uptake 103
Nutrient storage and metabolism 104
Vascular and antiinflammatory effects 106
Mitogenic action 107
Insulin-like growth factor 108
Insulin and IGF impact on cell longevity 111
Amylin 113
Glucagon 113
Conclusion 113
Bibliography 114
6 Oxidative Stress 120
Free radicals 120
Oxidases 120
Sources for free radicals 123
Endogenous antioxidants 124
Physiologic functions of oxidative stress 126
Mechanisms of oxidative damage 127
Cellular stress-sensitive pathways 127
Cellular targets of oxidative stress 128
Oxidative stress-related diseases 129
Endothelial dysfunction with oxidative stress 129
Cardiovascular disease 130
Insulin resistance and type 2 DM 131
Conclusion 133
Bibliography 134
7 Mental Stress 139
Stress responses 139
Central stress pathways 139
Peripheral stress pathways 140
Fight-flight-fright responses to acute stress 142
Sequelae of sustained passive stress 142
Inflammatory effects of stress pathways 143
Vascular and lipoprotein effects of
stress pathways 143
Stress impact on body weight 146
Metabolic effects of stress pathways 146
Depression and other mood disturbances 149
Conclusion 152
Bibliography 153
8 Sleep 159
Stages of sleep 159
Cardiovascular parameters during normal sleep 160
Function of sleep 161
Sleep duration 164
Circadian rhythm 165
Examples of circadian regulation 166
Neurohormonal modulation of wakefulness 168
Neurohormonal modulation of sleep 170
Sleep-arousal transitions 172
Sleep deficit 174
Pathophysiologic effects of sleep debt 175
Sleep debt and risk of cardiometabolic disorder 177
Sleep disorders 179
Conclusion 182
Bibliography 183
9 Inflammation 192
Immune responses 192
Selected participants in the inflammatory response 193
C-reactive protein 198
The renin-angiotensin-aldosterone system and inflammation 199
Inflammation and chronic diseases 202
Inflammation endothelial and vascular dysfunction 202
Inflammation and atherosclerosis 205
Acute inflammation carbohydrate metabolism and dyslipidemia 210
Chronic inflammation and the metabolic syndrome 213
Causes for systemic inflammation 215
Conclusion 218
Bibliography 219
10 Adipose Tissue and Overweight 228
Energy storage 228
Diverse fat depots 230
Adipose tissue as immune organ 234
Adipose tissue as endocrine organ 236
Adipokines with beneficial cardiometabolic effect 237
Adipokines with detrimental cardiometabolic effect 244
Obesity comorbidities and cardiovascular disease 250
Obesity insulin resistance and diabetes 252
Conclusion 254
Bibliography 255
11 Weight Loss and Diet 266
Homeostatic responses to weight gain and weight loss 266
Adipose weight loss effects 267
Antiinflammatory vasculoprotective and metabolic effects of weight loss
267
Dietary intervention for weight loss 269
Calorie restriction 270
Surgical intervention 277
Diet 279
Exercise as adjunct to weight loss 289
Conclusion 289
Bibliography 291
12 Skeletal Muscle and Exercise 303
Myocyte structure and function 303
Metabolic adaptations in skeletal muscle 305
Energy sensors 311
Skeletal muscle in inflammation 317
Skeletal muscle in insulin resistance 318
Exercise effect on inflammation and oxidative stress 320
Exercise effect on metabolism in obesity 322
Exercise effect and cardiovascular health 322
Exercise and insulin resistance 325
Exercise and mortality 328
Exercise recommendation 331
Conclusion 332
Bibliography 334
13 Lipids Atherogenic Dyslipidemia and Therapy 347
Apolipoproteins 347
Lipoproteins 347
Apo A-containing lipoproteins 348
Apo B-containing lipoproteins 355
Apolipoproteins C D and E 360
The triglyceride lipase family 360
The normal metabolism of free fatty acids 363
Inflammation and hepatic insulin resistance 365
Atherogenic dyslipidemia in insulin resistance 369
Lipid-lowering therapy 372
The HMG CoA reductase inhibitors 374
Nicotinic acid 387
The fibric acid derivatives 388
Bile acid sequestrants 391
Ezetimibe 391
CETP inhibition 391
Conclusion 392
Bibliography 393
14 The Endothelium Cardiovascular Disease and Therapy 409
Endothelial function 409
Nitric oxide synthase and eNOS 409
Endothelial NO synthesis 410
Specific enhancers of NO synthesis 413
Functions of nitric oxide 415
Shear stress and vascular function 418
Mechanisms of endothelial dysfunction 420
Insulin insulin resistance and endothelial dysfunction 424
Implications of endothelial dysfunction 428
Assessment of endothelial function 430
Hypertension 432
Cardiomyopathy 434
Coronary and peripheral vascular disease 440
Pharmacologic antagonism of the renin-angiotensin-aldosterone system and
endothelin-1 443
Beta-adrenergic blockade 448
Phosphodiesterase-5 inhibitors 449
Conclusion 450
Bibliography 451
15 Insulin Resistance Metabolic Syndrome and Therapy 468
Diagnostic criteria for the metabolic syndrome 468
Prevalence of the metabolic syndrome 470
Insulin resistance 470
Causes of insulin resistance 474
Pathways toward insulin resistance 476
Pharmacologic therapy to improve insulin sensitivity 480
Conclusion 483
Bibliography 484
Index 491
List of Abbreviations ix
1 The Metabolic Syndrome: A Relevant Concept? 1
2 Mitochondria 3
Background 3
Cellular respiration 6
Modulation of mitochondrial metabolic activity 9
Factors that affect mitochondrial number and activity 10
Peroxisome proliferator-activated receptor gamma coactivator-1 11
Mitochondrial production of prooxidant species 12
Mitochondria and nitric oxide 15
Mitochondrial calcium homeostasis 17
The mitochondrial permeability transition 18
Apoptosis 22
Causes for mitochondrial dysfunction 22
Implications of mitochondrial dysfunction 27
Mitochondrial dysfunction and cardiovascular disease 27
Mitochondrial dysfunction and metabolic disease 29
Conclusion 32
Bibliography 34
3 Telomeres 40
Telomere structure 40
Telomere function 41
Telomere shortening 41
Telomere dysfunction 42
Physiologic age 42
Gender differences 43
Telomerase 43
Cell senescence and apoptosis 46
Telomeres in aging 49
Risk factors for cardiometabolic disease 51
Telomeres senescence and chronic disease 54
Cardiovascular disease 54
Insulin resistance and type 2 DM 57
Conclusion 58
Bibliography 60
4 The FoxO Transcription Factors and Sirtuins 64
Forkhead transcription factors 64
Functions of FoxO 68
Cardiovascular forkhead effects 70
Metabolic forkhead effects 72
Histone acetylation and deacetylation 75
Sirtuin deacetylases 76
Sirtuin regulation 78
Antiinflammatory cardiovascular and myocyte sirtuin effects 80
Sirtuin effects on metabolism 81
Sirtuins and cell longevity 83
Forkhead deregulation and insulin resistance 85
Paradoxical effect of nutrition versus stress on cell death suppression
87
Conclusion 89
Bibliography 90
5 Insulin and Insulin-Like Growth Factor 96
Anabolism and catabolism 96
Control of plasma glucose 96
Insulin 97
Insulin receptor location 98
Metabolic insulin signaling 101
Insulin-mediated glucose uptake 103
Nutrient storage and metabolism 104
Vascular and antiinflammatory effects 106
Mitogenic action 107
Insulin-like growth factor 108
Insulin and IGF impact on cell longevity 111
Amylin 113
Glucagon 113
Conclusion 113
Bibliography 114
6 Oxidative Stress 120
Free radicals 120
Oxidases 120
Sources for free radicals 123
Endogenous antioxidants 124
Physiologic functions of oxidative stress 126
Mechanisms of oxidative damage 127
Cellular stress-sensitive pathways 127
Cellular targets of oxidative stress 128
Oxidative stress-related diseases 129
Endothelial dysfunction with oxidative stress 129
Cardiovascular disease 130
Insulin resistance and type 2 DM 131
Conclusion 133
Bibliography 134
7 Mental Stress 139
Stress responses 139
Central stress pathways 139
Peripheral stress pathways 140
Fight-flight-fright responses to acute stress 142
Sequelae of sustained passive stress 142
Inflammatory effects of stress pathways 143
Vascular and lipoprotein effects of
stress pathways 143
Stress impact on body weight 146
Metabolic effects of stress pathways 146
Depression and other mood disturbances 149
Conclusion 152
Bibliography 153
8 Sleep 159
Stages of sleep 159
Cardiovascular parameters during normal sleep 160
Function of sleep 161
Sleep duration 164
Circadian rhythm 165
Examples of circadian regulation 166
Neurohormonal modulation of wakefulness 168
Neurohormonal modulation of sleep 170
Sleep-arousal transitions 172
Sleep deficit 174
Pathophysiologic effects of sleep debt 175
Sleep debt and risk of cardiometabolic disorder 177
Sleep disorders 179
Conclusion 182
Bibliography 183
9 Inflammation 192
Immune responses 192
Selected participants in the inflammatory response 193
C-reactive protein 198
The renin-angiotensin-aldosterone system and inflammation 199
Inflammation and chronic diseases 202
Inflammation endothelial and vascular dysfunction 202
Inflammation and atherosclerosis 205
Acute inflammation carbohydrate metabolism and dyslipidemia 210
Chronic inflammation and the metabolic syndrome 213
Causes for systemic inflammation 215
Conclusion 218
Bibliography 219
10 Adipose Tissue and Overweight 228
Energy storage 228
Diverse fat depots 230
Adipose tissue as immune organ 234
Adipose tissue as endocrine organ 236
Adipokines with beneficial cardiometabolic effect 237
Adipokines with detrimental cardiometabolic effect 244
Obesity comorbidities and cardiovascular disease 250
Obesity insulin resistance and diabetes 252
Conclusion 254
Bibliography 255
11 Weight Loss and Diet 266
Homeostatic responses to weight gain and weight loss 266
Adipose weight loss effects 267
Antiinflammatory vasculoprotective and metabolic effects of weight loss
267
Dietary intervention for weight loss 269
Calorie restriction 270
Surgical intervention 277
Diet 279
Exercise as adjunct to weight loss 289
Conclusion 289
Bibliography 291
12 Skeletal Muscle and Exercise 303
Myocyte structure and function 303
Metabolic adaptations in skeletal muscle 305
Energy sensors 311
Skeletal muscle in inflammation 317
Skeletal muscle in insulin resistance 318
Exercise effect on inflammation and oxidative stress 320
Exercise effect on metabolism in obesity 322
Exercise effect and cardiovascular health 322
Exercise and insulin resistance 325
Exercise and mortality 328
Exercise recommendation 331
Conclusion 332
Bibliography 334
13 Lipids Atherogenic Dyslipidemia and Therapy 347
Apolipoproteins 347
Lipoproteins 347
Apo A-containing lipoproteins 348
Apo B-containing lipoproteins 355
Apolipoproteins C D and E 360
The triglyceride lipase family 360
The normal metabolism of free fatty acids 363
Inflammation and hepatic insulin resistance 365
Atherogenic dyslipidemia in insulin resistance 369
Lipid-lowering therapy 372
The HMG CoA reductase inhibitors 374
Nicotinic acid 387
The fibric acid derivatives 388
Bile acid sequestrants 391
Ezetimibe 391
CETP inhibition 391
Conclusion 392
Bibliography 393
14 The Endothelium Cardiovascular Disease and Therapy 409
Endothelial function 409
Nitric oxide synthase and eNOS 409
Endothelial NO synthesis 410
Specific enhancers of NO synthesis 413
Functions of nitric oxide 415
Shear stress and vascular function 418
Mechanisms of endothelial dysfunction 420
Insulin insulin resistance and endothelial dysfunction 424
Implications of endothelial dysfunction 428
Assessment of endothelial function 430
Hypertension 432
Cardiomyopathy 434
Coronary and peripheral vascular disease 440
Pharmacologic antagonism of the renin-angiotensin-aldosterone system and
endothelin-1 443
Beta-adrenergic blockade 448
Phosphodiesterase-5 inhibitors 449
Conclusion 450
Bibliography 451
15 Insulin Resistance Metabolic Syndrome and Therapy 468
Diagnostic criteria for the metabolic syndrome 468
Prevalence of the metabolic syndrome 470
Insulin resistance 470
Causes of insulin resistance 474
Pathways toward insulin resistance 476
Pharmacologic therapy to improve insulin sensitivity 480
Conclusion 483
Bibliography 484
Index 491