1. MCB 135K: Discussion

2. Significance of Age Changes in the Vascular Endothelium
Significance of Age Changes in the Vascular Endothelium *Table 16-2, page 293*
Endothelial cells line the internal wall (intima) of the blood vessels.
While the muscle cells and the elastic fibers in the vascular wall regulate blood vessel motility (contraction and relaxation), the endothelial cells, serve as protective lining against trauma, infections, etc,
Endothelial cells undergo significant changes with aging indicative of abnormal function.
These alterations by themselves may induce pathology or may predispose with other factors to atherosclerosis

3. Significance of Age Changes in the Vascular Endothelium
Significance of Age Changes in the Vascular Endothelium *Table 16-2, page 293*
Endothelial cells undergo significant changes indicative of abnormal function
The imbalance of vascular tone is manifested by increased vasoconstriction
Endothelins EDRF, NO
Vascular integrity (cell proliferation and migration, wall remodeling) and injury repair through local growth factors are impaired
VEGF Cytokines
Maintenance of blood fluidity is disrupted with increased cell adherence, blood coagulation, and thrombogenic properties
Cytokines
These alterations by themselves may induce pathology or may predispose with other factors to atherosclerosis

4. Table 16-8: Theories of Atherosclerosis
Lipid accumulation
Myoclonal
Thrombogenic
Inflammation
Free Radicals
**See page 299**

6. High homocysteinemia and Protein C

7. Lipids and Apolipoproteins
Major Categories
Risk Factors in Atherosclerosis
Lipoprotein Synthesis
Apolipoproteins
Lipolytic Enzymes
Receptors

8. Lipids and Apolipoproteins
Categories
Chylomicrons and VLDL
High triglycerides
IDL and LDL
High cholesterol
HDL
High proteins
High phospholipid

10. Lipids and Apolipoproteins
Risk Factors
Total cholesterol to HDL ratio above 4.0
Family history
Elevated LDL; Low HDL
Diabetes Mellitus
Age
Hypertension
Obesity
Smoking

11. Lipoprotein Synthesis
Intestine CM
Nascent HDL
Liver
VLDL
IDL
LDL

12. Apolipoproteins Definition: Roles in Metabolism
Markers on lipid cell surface that determines metabolic fate of lipids
Roles in Metabolism
apoA-I
HDL
Reverse Cholesterol Transport
apoB-100
VLDL, IDL, LDL
Sole protein on LDL
Necessary for assembly and secretion in liver
Ligand for LDL receptorapoA-I is important in reverse cholesterol transport (review figure 17.3)
Process whereby lipid free apoA-I and subclasses of HDL mediate the removal of excess cholesterol

13. Apolipoproteins and RCT
apoA-I is important in reverse cholesterol transport (review figure 17.3)
Process whereby lipid free apoA-I and subclasses of HDL mediate the removal of excess cholesterol

14. Enzymes Lipoprotein Lipase Hepatic Triglyceride LCAT
Catabolizes CM and VLDL produces glycerol and fatty acids
Requires apoC-II for activation
Hepatic Triglyceride
LCAT
Essential for normal maturation of HDL
Associates with discoidal HDL and is activated by apoA-I
Forms hydrophobic cholesteryl ester that moves to core and gives spheroid shape (active)

15. Receptors LDL Macrophage Scavenger (SR-A1) SR-B1
Responsible for internalization of LDL
Also known as apoB-E receptor
Regulates cholesterol synthesis
Macrophage Scavenger (SR-A1)
Recognizes oxidized LDL
Role in atherogenesis
SR-B1
Docking protein for HDL
Role in selective uptake for steroid hormone production
Role in catabolism and excretion from liver

16. Exercise and Aging Cardiovascular Fitness Metabolic Fitness
Muscular Strength
Anti-oxidant defenses

17. Exercise and Aging Cardiovascular Fitness Maximal oxygen consumption
VO2 Max increased by regular exercise
Declines with aging
Decreases morbidity
Decreases mortality

18. Exercise and Aging Metabolic Fitness
Control age related increases in body fat
Decrease risk of diabetes
Maintain Ideal BMI
Exercise at 45-50% of VO2 Max to facilitate fat loss (utilize fat as energy source)