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Prevalence of Cardiovascular Disease by Race American Heart Association
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Prevalence of Cardiovascular Disease American Heart Association
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Clean Artery Clean Artery Fatty Steaks Fibrous Plaque Clinical Lesion NATURAL HISTORY OF ATHEROSCLEROSIS
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Lumen Subendothelial Space
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NO L-arginine O 2 NADPH Lumen ↑NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasodilation Nitric Oxide
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NO L-arginine O 2 NADPH Lumen ↑NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasodilation Oxidative Stress O2-O2- ONOO -
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NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasodilation Oxidative Stress O2-O2- ↓NO ONOO -
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NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasoconstriction Oxidative Stress O2-O2- ↓NO ONOO -
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NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasoconstriction Oxidative Stress O2-O2- ↓NO ONOO - O2-O2-
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ENDOTHELIAL FUNCTION VASODILATION
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Shear Stress PI-3-Kinase Oxygen L-Arginine NADPH Oxygen L-Arginine NADPH Nitric Oxide Nitric Oxide eNOS Cofactors
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VASODILATION Shear Stress PI-3-Kinase Oxygen L-Arginine NADPH Oxygen L-Arginine NADPH Nitric Oxide Nitric Oxide eNOS Cofactors NO i cGMP ↓Ca ++
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ARTERIAL HEALTH Flow-Mediated Dilation Pre
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ARTERIAL HEALTH Flow-Mediated Dilation = 8% Pre Post 4.1 mm 4.7 mm
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Faulx, et al, American Heart Journal 145:943-951, 2003 Iiyama, et al. American Heart Journal 132:779-782, 1996 Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22:477-484, 1998. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994. Faulx, et al, American Heart Journal 145:943-951, 2003 Iiyama, et al. American Heart Journal 132:779-782, 1996 Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22:477-484, 1998. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994.
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Hasimoto, et al. Circulation 92:3431-3435, 1995. Apparently Healthy
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Woo, et al, International Journal of Obesity 28:852-857, 2004 Children
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Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994. Aging
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Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22:477-484, 1998. Overweight & Obesity
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Iiyama, et al. American Heart Journal 132:779-782, 1996 Hypertension
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Caballero, A.E., Obesity Research 11:1278-1289, 2003. Diabetes
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NO L-arginine O 2 NADPH Lumen ↑NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Resistance Acetylcholine Anti-Adhesion Anti-Coagulation Fibrinolysis Vasodilation
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NO L-arginine O 2 NADPH Lumen Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine ↓NO Anti-Adhesion Anti-Coagulation Fibrinolysis ↑NO Vasodilation
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NO L-arginine O 2 NADPH Lumen Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine ↓NO Anti-Adhesion Anti-Coagulation Fibrinolysis Vasoconstriction
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Celemajer, D, et al Circulation 88:2149-2155, 1999 Endothelial Function of Smokers
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Celemajer, D, et al Circulation 88:2149-2155, 1999 Endothelial Function of Smokers
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OXIDATIVE STRESS IN OBESITY Davi, et al. JAMA 288:2008-2014, 2002
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OXIDATIVE STRESS FOLLOWING MAXIMAL EXERCISE Vincent, et al. Med Sci Sport Sci, 37:213-219, 2005.
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Triglyceride StorageTriglyceride Release Resistin TNF - α Adiponectin Plasminogen activator inhibitor Leptin Agiotensin Adipocyte
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Exercise
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Tsai, et al. Clinical Science 106:315-319, 2004 Anderson, et al, Atherosclerosis 154:475-483, 2001 Ceriello, et al, Circulation 106:1211-1218, 2002 Tsai, et al. Clinical Science 106:315-319, 2004 Anderson, et al, Atherosclerosis 154:475-483, 2001 Ceriello, et al, Circulation 106:1211-1218, 2002
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Β Oxidation ↑Electron Donors Electron Transport Chain ↑FADH 2 ↑ O 2 - TCA Cycle ↑ FFA ↑ NADH+H + NAD + e-e- Complex I Complex III Complex II Complex IV Q-Q- e-e- e-e- e-e- FAD
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Hamby et al, Diabetes Care 26:2119-2125, 2003 Watts, et al, Journal Pediatrics 144:620-625, 2004 Walsh, et al, JAP 95:20-25, 2003 Hamby et al, Diabetes Care 26:2119-2125, 2003 Watts, et al, Journal Pediatrics 144:620-625, 2004 Walsh, et al, JAP 95:20-25, 2003 EXERCISE IMPROVES ENDOTHELIAL FUNCTION
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NITRIC OXIDE i Eight weeks of training in healthy adults Maeda, et al. Life Sciences 69:1005-1016, 2001
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Padilla, et al., European Journal of Applied Physiology, 98:256-262, 2006
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Johnson, B. et al. ACTIVE vs. INACTIVE
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Johnson, B. et al. ACTIVE vs. INACTIVE
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Johnson, B. et al. ACTIVE vs. INACTIVE
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Johnson, B. et al. ACTIVE vs. INACTIVE
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Johnson, B. et al. ACTIVE vs. INACTIVE
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Harris, et al, Obesity, 2008 Active & Inactive Overweight Men Active & Inactive Overweight Men FMD Response Treadmill Exercise Treadmill Exercise
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Oxidative Source Oxidative Stress ( 8 PG F2alpha) Endothelial Function Single Physical Activity Session NO bioavailability Blood Flow Anti- inflammatory Myokine ( IL-6) Inflammatory Stress ( TNF-alpha) Antioxidant Defense ( SOD) Insulin Resistance Visceral Fat ( TNF-alpha) Systemic Inflammation ( CRP) Habitual Physical Activity Insulin Resistance
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