1. Prevalence of Cardiovascular Disease by Race American Heart Association

5. Prevalence of Cardiovascular Disease American Heart Association

6. Clean Artery Clean Artery Fatty Steaks Fibrous Plaque Clinical Lesion NATURAL HISTORY OF ATHEROSCLEROSIS

10. Lumen Subendothelial Space

11. 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

12. 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 -

13. 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 -

14. 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 -

15. 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-

20. ENDOTHELIAL FUNCTION VASODILATION

22. Shear Stress PI-3-Kinase Oxygen L-Arginine NADPH Oxygen L-Arginine NADPH Nitric Oxide Nitric Oxide eNOS Cofactors

23. VASODILATION Shear Stress PI-3-Kinase Oxygen L-Arginine NADPH Oxygen L-Arginine NADPH Nitric Oxide Nitric Oxide eNOS Cofactors NO i cGMP ↓Ca ++

24. ARTERIAL HEALTH Flow-Mediated Dilation Pre

25. ARTERIAL HEALTH Flow-Mediated Dilation = 8% Pre Post 4.1 mm 4.7 mm

26. 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.

27. Hasimoto, et al. Circulation 92:3431-3435, 1995. Apparently Healthy

28. Woo, et al, International Journal of Obesity 28:852-857, 2004 Children

29. Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994. Aging

30. Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22:477-484, 1998. Overweight & Obesity

31. Iiyama, et al. American Heart Journal 132:779-782, 1996 Hypertension

32. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Diabetes

33. 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

34. 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

35. 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

36. Celemajer, D, et al Circulation 88:2149-2155, 1999 Endothelial Function of Smokers

37. Celemajer, D, et al Circulation 88:2149-2155, 1999 Endothelial Function of Smokers

38. OXIDATIVE STRESS IN OBESITY Davi, et al. JAMA 288:2008-2014, 2002

39. OXIDATIVE STRESS FOLLOWING MAXIMAL EXERCISE Vincent, et al. Med Sci Sport Sci, 37:213-219, 2005.

42. Triglyceride StorageTriglyceride Release Resistin TNF - α Adiponectin Plasminogen activator inhibitor Leptin Agiotensin Adipocyte

43. Exercise

46. 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

49. 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

50. 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

51. NITRIC OXIDE i Eight weeks of training in healthy adults Maeda, et al. Life Sciences 69:1005-1016, 2001

56. Padilla, et al., European Journal of Applied Physiology, 98:256-262, 2006

57. Johnson, B. et al. ACTIVE vs. INACTIVE

58. Johnson, B. et al. ACTIVE vs. INACTIVE

59. Johnson, B. et al. ACTIVE vs. INACTIVE

60. Johnson, B. et al. ACTIVE vs. INACTIVE

61. Johnson, B. et al. ACTIVE vs. INACTIVE

62. Harris, et al, Obesity, 2008 Active & Inactive Overweight Men Active & Inactive Overweight Men FMD Response Treadmill Exercise Treadmill Exercise

63. 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