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Atherosclerosis
and Heart Attacks
Atherosclerosis is the
major cause of coronary artery disease and stroke. It is a progressive,
degenerative disease that leads to the blockage of small arteries.
Blood flow through effected arteries is diminished and may eventually
become completely blocked. Occlusion (blockage) of the artery is
due to the development of a fatty plaque. The plaque protrudes
into the lumen (open space) of the artery, thus diminishing
blood flow in the artery.
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The formation of plaques
occurs in a sequential fashion. First, cholesterol-rich lipids (fat)
infiltrate the lining of the blood vessel and are deposited within
the wall of a blood vessel. Next, abnormal smooth muscle cells migrate
to the site of the developing plaque, causing a bulge that narrows
the lumen of the artery. This is followed by the formation of a connective
tissue cap (scar tissue) over the developing plaque. Eventually the
plaque becomes hardened by deposition of calcium salts. |
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If the lining of the
vessel overlying the plaque becomes damaged (ulceration) the plaque
may rupture, thus exposing blood to the interior of the plaque.
Connective tissue (collagen) in the plaque stimulates the activation
of platelets, thus leading to the formation of a blood clot. If
the clot remains in place it is called a thrombus. If the
clot breaks away and travels to another site it is called an embolus.
The formation of a blood clot can lead to sudden occlusion of an
artery. Occlusion of a coronary artery may lead to heart attack
(myocardial infarction), while occlusion of a artery in the
brain can lead to stroke.
Drugs that dissolve clots
(clot busters) are used as treatment for acute myocardial infarction
and stroke. Tissue plasminogen activator (TPA) is a human
protein that facilitates the breakdown of blood clots. The gene
that encodes TPA was cloned by a local biotechnology company, Amgen.
Recombinant TPA is now available as a clinical drug. Although its
expensive ($2000 dollars per dose), its very effective at breaking
blood clots and saving lives. After Amgen looses its patent on TPA
(15 years) the drug price will drop significantly. Streptokinase
is another enzyme that dissolves blood clots. This not a human enzyme,
but rather a streptococcus bacterial enzyme. Streptokinase is purified
out of bacteria and packaged in pure form. Streptokinase is cheap
($2 dollars per dose) and effective, but may only be used a few
times before the immune system renders it ineffective.
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Risk
Factors for Atherosclerosis
The cause of atherosclerosis
is not entirely clear. However there are certain risk factors that
increase (statistically) one's chances of acquiring the disease.
Risk factors for atherosclerosis include:
- genetic predisposition
- obesity
- age
- smoking
- hypertension
- diabetes
- high blood cholesterol
Of all the risk factors,
high blood levels of cholesterol are the most significant. Cholesterol
(shown as a yellow dot in the figure below) is an essential steroid.
It is found in the plasma membrane of all cells and is the precursor
to all steroid hormones. Blood levels of cholesterol are regulated
by the liver. If cholesterol is absent from the diet, then the liver
will synthesize it from fatty acids (red squares in figure below).
If blood levels of cholesterol are excessive then the liver will
secrete it into bile, which is then delivered to the small intestine
and eliminated with the feces.
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a lipid, it does not dissolve into the aqueous fluid of the blood.
Cholesterol is transported in the blood bound to lipoproteins, which
are soluble in the blood. LDLs (low-density lipoproteins) carry
cholesterol from the liver to the cells. HDLs (high-density
lipoproteins) carry cholesterol from the cells to the liver for excretion.
High levels of LDL correlate with a higher incidence of atherosclerosis.
This may be because the liver is sending too much cholesterol out
into the body. Thus LDL is considered the "bad" cholesterol. High
levels of HDL are correlated with a lower incidence of atherosclerosis.
This may be because HDLs function to send cholesterol back to the
liver for excretion, effectively lowering blood cholesterol. Thus
HDL is considered the "good" cholesterol. |
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LDLs that have been oxidized
by free radicals (highly reactive electron-deficient molecules)
are considered to be the "worst" cholesterol. Antioxidants
are chemicals that "soak up" free radicals before they
can do much harm. Dietary intake of antioxidants, such as vitamin
E, vitamin C, and beta-carotene has been shown to slow plaque deposition.
One can significantly
lower blood levels of cholesterol, and therefore lower the risk
of developing atherosclerosis, by limiting dietary intake of cholesterol.
Also, absorption of dietary cholesterol can be limited by eating
indigestible fibers such as oat bran, which inhibits the uptake
of cholesterol from the food in the small intestine.
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Coronary
Artery Disease
Although a tremendous
amount of blood flows through the chambers of the heart, this blood
does not nourish the heart. The heart is nourished by blood from
the coronary circulation, a system of arteries, capillaries
and veins that brings blood to all of the tissues of the heart.
As one begins to exercise, the heart works harder and therefore
requires more oxygen. As oxygen demands of the heart increase, vasodilation
of coronary arteries supplies more blood, thus meeting the demand.
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Normally, coronary blood
flow can keep pace with increased oxygen demands during exercise.
However, if the coronary arteries are partially blocked by atherosclerotic
plaques, as is observed in coronary artery disease, then
blood flow through the coronary arteries may not be sufficient to
supply the level of oxygen required. In this case, heart muscle
cells may experience ischemia (lack of oxygen). In the absence
of oxygen cardiac cells shift to anaerobic respiration of glucose
and produce lactic acid as a by-product. Lactic acid is thought
to stimulate pain receptors. This pain in the chest, due to ischemia,
is referred to as Angina Pectoris. The symptoms of angina
pectoris reoccur whenever oxygen demand out-paces oxygen supply,
for example, during exercise or stress. Vasodilators, such as nitroglycerin,
are effective in treating angina pectoris because they open blood
vessels occluded by plaques. Treatment
for severe coronary artery disease is bypass surgery. In
this procedure, a healthy blood vessel, removed from a different
part of the body, is grafted from the aorta to a region of the artery
just downstream of the occlusion.
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