Adhesion Molecules
Monocyte
Vessel Lumen LDL
Endothelium
LDL
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Cytokines
Oxidized LDL
Macrophage
Intima
Macrophages take up modified LDL
Monocyte
Adhesion Molecules
Different from arteriosclerosis (hardening of the arteries), which is due to calcification of the arterial wall.
Oxidized LDL Induces leukocyte “homing”
Etiology
• Mutations in the gene coding for LDL receptors
Protein synthesis, expost and import
Ways to get proteins into organelles or membranes
Co-translational import
Genetic factors are prevalent (like in familial hypercholesterolemia)
Familial Hypercholesterolemia
Incidence: 1 in 500 The most common known form of genetic disease Results in
Atherosclerosis: A disease of large and mediumsized arteries that results in progressive accumulation of smooth muscle cells and lipids within the intima. Typically kills by inducing myocardial infarction
Etiology
Fatty streaks are typically found in teenagers, so the disease begins early. Occurrence increases with
• obesity • diabetes • high lipid/cholesterol diets • increasing age • high blood pressure
• 2X to 6X increase in serum cholesterol • Severe and early atherosclerosis and myocardial infarction • Diagnosed on the above two items, and a family history
Estimated 2001 CVD cost = $300 billion ($180 billion in direct health care costs) 3/4 of all CVD deaths are the result of atherosclerosis.
Intima - endothelial cells and the internal elastic lamina
Media - consists of smooth muscle cells and more elastic layers
Adventitia - consists of connective tissue, fat cells, nerves and other stuff
Definition
• Put proteins into organelles or membranes during the actual process of translation
• Examples: extracellular proteins, cell membranes, lysosomal enzymes
Post-translational import
• Make proteins in the cytoplasm, and subsequently import them into the organelle of choice
• Examples: the nucleus, the mitochondrion
CVD
Half of all Americans die from cardiovascular disease (CVD)
• Ischemic (Coronary) Heart Disease • Hypertensive Disease • Rheumatic Fever / Rheumatic Heart Disease • Cerebrovascular Disease (Stroke)
Necrosis frees the modified LDL
Vessel Lumen
LDL
Endothelium
LDL
Foam Cell
Oxidized LDL Taken up by Macrophage
Macrophage
Intima
Foam cells and macrophages
Etiology
What is the "trigger" for initiation of the disease?
• Hemodynamic stress • Bacterial infection, particularly periodontal disease • High lipid cocentrations
Each is directed by “signals” embedded in the amino acid sequence of the newly synthesized protein
Co-translational import of proteins