Transcript Slide 1

Prevalence of Cardiovascular Disease by Race
Whole
Caucasians
African Americans
Hispanics
Women
Men
0
10
20
30
40
Prevalence of CVD (%)
American Heart Association
50
60
Prevalence of Cardiovascular Disease
Prevalence of CVD (%)
38
37
36
35
Men
Women
34
33
32
2002
2005
Year
American Heart Association
NATURAL HISTORY OF ATHEROSCLEROSIS
Clinical
Lesion
Fatty
Steaks
Clean
Artery
Fibrous
Plaque
Lumen
Subendothelial
Space
Blood Flow
Insulin
Acetylcholine
Lumen
↑NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
eNOS
NO
BH4
Subendothelial
Space
Nitric
Oxide
↑NO
Vasodilation
Blood Flow
Insulin
Acetylcholine
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
Oxidative
Lumen Stress
↑NO
PI-3 kinase
NADPH
L-arginine
O2
O2-
eNOS
NO
BH4
ONOO-
Subendothelial
Space
↑NO
Vasodilation
Blood Flow
Insulin
Acetylcholine
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
Oxidative Stress
↓NO
PI-3 kinase
NADPH
L-arginine
O2
O2-
eNOS
NO
BH4
ONOO-
Subendothelial
Space
↓NO
Vasodilation
Blood Flow
Insulin
Acetylcholine
Oxidative Stress
↓NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
O2-
eNOS
NO
BH4
ONOO-
Subendothelial
Space
↓NO
Vasoconstriction
Ross, New England Journal of Medicine, 340:115-126, 1999.
ENDOTHELIAL FUNCTION
VASODILATION
VASODILATION
VASODILATION
Shear Stress
PI-3-Kinase
eNOS
Oxygen
L-Arginine
NADPH
Nitric
Oxide
Cofactors
VASODILATION
Shear Stress
i
PI-3-Kinase
↓Ca++
eNOS
Oxygen
L-Arginine
NADPH
Nitric
Oxide
Cofactors
cGMP
NO
ARTERIAL HEALTH
Pre
Flow-Mediated Dilation
ARTERIAL HEALTH
Pre
Pre
4.1 mm
Post
4.7 mm
Flow-Mediated Dilation = 8%
10
FMD (%)
8
6
4
2
Healthy
Aging
Heart Disease
Visceral Fat
Diabetes
Hypertension
0
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.
Apparently Healthy
18
16
14
12
10
FMD (%)
8
6
4
2
0
Hasimoto, et al. Circulation 92:3431-3435, 1995.
Men
Women
Children
Children
12
10
8
FMD (%) 6
4
2
0
Woo, et al, International Journal of Obesity 28:852-857, 2004
Normal Weight
Obese
Aging
12
10
8
Men
Women
FMD (%) 6
4
2
0
20 30 40 50 60 65 70
Years
Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994.
Overweight & Obesity
9
8
7
6
5
FMD (%)
4
3
2
1
0
Normal
Subcutaneuous
Visceral Fat
Hashimoto, et al. International Journal of Obesity: Relar Metab Disord
22:477-484, 1998.
Hypertension
20
15
FMD (%) 10
5
0
Iiyama, et al. American Heart Journal 132:779-782, 1996
Normal Blood
Pressure
High Blood
Pressure
Diabetes
FMD (%)
14
12
10
8
6
4
2
0
Caballero, A.E., Obesity Research 11:1278-1289, 2003.
Normal
Glucose
Intolerance
Diabetes
Blood Flow
Insulin
Acetylcholine
Oxidative Stress
↓NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
O2-
eNOS
NO
BH4
O2ONOO-
Subendothelial
Space
↓NO
Vasoconstriction
Endothelial Function of Smokers
12
10
FMD (%)
8
6
4
2
0
Non-Smokers
Current Smokers
Past Smokers
Celemajer, D, et al Circulation 88:2149-2155, 1999
Endothelial Function of Smokers
12
FMD (%)
10
8
6
4
2
0
Celemajer, D, et al Circulation 88:2149-2155, 1999
OXIDATIVE STRESS IN OBESITY
600
8 PGF2alpha (pg/ml)
500
400
Nonobese
300
Gynoid Obesity
Andriod Obesity
200
100
0
Davi, et al. JAMA 288:2008-2014, 2002
Lipid Hydroperoxides (nmol/ml)
OXIDATIVE STRESS FOLLOWING MAXIMAL
EXERCISE
3.5
*
3
2.5
2
Pre
1.5
Post
1
0.5
0
Non Obese
Obese
Vincent, et al. Med Sci Sport Sci, 37:213-219, 2005.
Brachial Artery FMD (%)
10
9
8
7
6
5
4
3
2
1
0
Healthy
Healthy
Diabetes
Pre-Meal
Post-Meal
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
10
9
8
FMD (%)
7
6
Healthy
Aging
Heart Disease
5
Visceral Fat
4
Diabetes
3
2
1
0
Hypertension
10
9
FMD (%)
8
Healthy
Aging
7
Heart Disease
6
Visceral Fat
5
Diabetes
Hypertension
4
3
Healthy Postprandial
2
Diseased Postprandial
1
0
Blood Flow
Lumen
Insulin Resistance
Acetylcholine
↑NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
eNOS
NO
BH4
Subendothelial
Space
↑NO
Vasodilation
Blood Flow
Lumen
Insulin
Acetylcholine
↓NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
eNOS
NO
BH4
Subendothelial
Space
↑NO
Vasodilation
Blood Flow
Lumen
Insulin
Acetylcholine
↓NO
Anti-Adhesion
Anti-Coagulation
Anti- Fibrolysis
PI-3 kinase
NADPH
L-arginine
O2
eNOS
NO
BH4
Subendothelial
Space
↓NO
Vasoconstriction
EXERCISE IMPROVES ENDOTHELIAL FUNCTION
14
12
10
Pre-Training
Post-Training
Heart Dis
Diabetes
Met Synd
4
2
0
Ob Chld
6
OW
FMD (%)
8
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
VASODILATION
Eight weeks of training in healthy adults
i
60
NO (umol/L)
50
40
30
20
10
0
Before
After
Maeda, et al. Life Sciences 69:1005-1016, 2001
Arterial Health (FMD)
12
10
High Fat
8
Low Fat
6
HFM &
Exercise
4
2
0
Before
After
Padilla, et al., European Journal of Applied Physiology, 98:256-262, 2006
12
FMD (%)
10
8
Inactive
Active
6
4
2
0
Pre-Meal
Post-Meal
Padilla, et al. Medicine and Science in Sport and Exercise, in press.
SOD Activity
9.4
9.2
9
8.8
8.6
8.4
8.2
8
7.8
7.6
7.4
Inactive
Active
Pre-Meal
Post-Meal
Fly, et al. Medicine and Science in Sport and Exercise, in press.
Active & Inactive
Treadmill
Exercise
Overweight Men
FMD
Response
9
8
7
Sedentary
Active
FMD (%) 6
5
4
3
Baseline
Harris, et al, Obesity, 2008
Post Exercise
Habitual Physical Activity
High-Fat
Meal
Antioxidant
Defense
(SOD)
 Oxidative Stress
( 8 PG F2alpha)
Visceral Fat
( TNF-alpha)
Insulin
Resistance
Systemic
Inflammation
( CRP)
 NO
bioavailability
 Endothelial
Function
Single Physical Activity Session
Inflammatory Stress
( TNF-alpha)
Antiinflammatory
Myokine
( IL-6)
 Blood Flow