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

7. Lumen Subendothelial Space

8. NO L-arginine O 2 NADPH Lumen ↑NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasodilation Nitric Oxide

9. NO L-arginine O 2 NADPH Lumen ↑NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasodilation Oxidative Stress O2-O2- ONOO -

10. NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasodilation Oxidative Stress O2-O2- ↓NO ONOO -

11. NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasoconstriction Oxidative Stress O2-O2- ↓NO ONOO -

12. Ross, New England Journal of Medicine, 340:115-126, 1999.

13. ENDOTHELIAL FUNCTION VASODILATION

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

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

17. ARTERIAL HEALTH Flow-Mediated Dilation Pre

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

19. 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.

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

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

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

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

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

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

26. NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasoconstriction Oxidative Stress O2-O2- ↓NO ONOO - O2-O2-

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

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

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

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

31. 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

34. 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 Anti- Fibrolysis 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 Anti- Fibrolysis ↑NO Vasodilation

36. NO L-arginine O 2 NADPH Lumen Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine ↓NO Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasoconstriction

37. 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

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

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

40. Padilla, et al. Medicine and Science in Sport and Exercise, in press.

41. Fly, et al. Medicine and Science in Sport and Exercise, in press.

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

43. High-Fat Meal  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