Mechanism of Atherosclerosis – lecture notes

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, LDLs) and macrophages
within the wall of the vessel
C. This buildup results in plaque formation and obstruction of blood flow to
tissues


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

III. Mechanism of Atherosclerosis
A. Elevated levels of LDLs result in them becoming oxidized and damaged
B. Damaged LDLs cannot be taken up by cells and therefore remain in
blood – elevated levels of LDL’s
C. Damaged LDLs enter the underlining 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 the wall of vessels and
turn into hungry scavenger cells known as macrophages (literally, big eaters)
E. Macrophages eat the damaged LDLs 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 LDLs
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 LDLs
K. These damaged LDLs accumulate in the vessel wall which attracts
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 is 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