MCB 135K: Discussion

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

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

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

High homocysteinemia and Protein C

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

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

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

Lipoprotein Synthesis Intestine CM Nascent HDL Liver VLDL IDL LDL

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

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

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)

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

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

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

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)