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Mechanism of Atherosclerosis – lecture notes

By at September 29, 2011 | 6:48 am | Print

Atherosclerosis – #1 killer in the United States *coronary artery disease

I.  Disease of arteries (blood vessels that supply nutrients to tissue)
A. Dysfunction of the blood vessels lining
B. Leads to build up of lipids (low density lipoproteins, LDL’s) and macrophages
within wall of vessel
C. This buildup results in plague formation and obstruction of blood flow to
tissues

II. Lipoproteins
A. Lipid core surrounded by proteins to make it soluble
B. High density lipoproteins (HDL’s)
1. Take cholesterol from blood back to liver
2. “Good” cholesterol
C. Low density lipoproteins (LDL’s)
1. Takes cholesterol from liver to other tissues

III. Mechanism of Atherosclerosis
A. Elevated levels of LDL’s result in them becoming oxidized and damaged
B. Damaged LDL’s cannot be taken up by cells and therefore remain in
blood – elevated levels of LDL’s
C. Damaged LDL’s enter under lining of vessels and accumulate within
walls of vessels (often in coronary arteries which serve the heart tissue)
D. Monocytes (a type of white blood cell) enter into wall of vessels and
turn into hungry scavenger cells known as macrophages (literally, big eaters)
E. Macrophages eat the damaged LDL’s in the wall of the vessels
F. Macrophages eat so much that they become big white fatty cells (Foam
cells) that contribute to the fatty streak in the vessel wall
G. In this process, the macrophages produce free radicals (oxidizing
agents) that damage more LDL’s
H. The newly damaged LDL’s accumulate in the vessel wall
I.  This attracts more monocytes to the area which become macrophages
J.  These macrophages produce more damaging oxidizing agents which
damage more LDL’s
K. These damaged LDL’s accumulate in the vessel wall which attract
more monocytes
L. The vicious cycle continues until the vessel is severely altered
a. Unwanted clotting can occur (thrombus)
M. This deprives the heart tissue of blood and the heart tissue dies
N.  Myocardial Infarction (MI) a.k.a. Heart Attack – death of the heart
tissue

IV. Contributing factors
A. Hyperlipidemia
1. Diet high in saturated fats / cholesterol
2. High LDL to HDL levels
2. High triglycerides are associated with low HDL
3. Diabetes
B. Hypertension – high blood pressure
1. Adds to damage of vessel lining
C. Smoking
1. Affects lining and increases clotting

V. Prevention / Treatment
A. Diet
1. Low in saturated fat and cholesterol
2. Moderate alcohol intake reduces risk
B. Exercise
1. Increases HDL’s
2. Decreases blood pressure
3. Decreases body weight
C. Drugs
1. Lower cholesterol
2. Aspirin – 81 mg / day
a. Decreases abnormal clotting and inflammation of vessels

VI. Familial hypercholesterolemia
A. Autosomal dominant disorder
B. Heterozygous – 1 in 500 in U.S.
1. One copy of bad gene (hepatic LDL receptor)
2. Heart disease usually seen by age 50-60
C. Homozygous – 1 in million in U.S.
1. Inherited two bad genes
2. Heart disease seen in 20’s

 

 

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