By: Mehdi AlDahlaki

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Atherosclerosis
By Mehdi Al-Dahlaki
March 2005
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Im going to talk about - What is
atherosclerosis? - What are the consequences of
atherosclerosis? - What causes atherosclerosis? -
Types of atherosclerosis. - The Mendelian and
polygenic mutations causing atherosclerosis. With
examples from both.
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What is atherosclerosis? Greek athere ? gruel
skleros ? hard Also called arteriosclerosis,
referring to the Greek word arteria that means
artery. A disease that causes build ups of
substances, in the inner lining, called
endothelium, of an artery. These build ups are
also called plaques.
- deposit fatty substances - cholesterol -
cellular waste products - calcium - other
substances
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When a plaque is formed, the following can
happen I. Large plaques that reduce blood flow
in the arteries. II. Softened plaques that cause
blood clotting, Blood clotting ? Injury ?
Inflammation in the blood ? -heart attack
(blocking of a vessel feeding the heart with
blood) -stroke (blocking of a vessel feeding the
brain with blood) - Difficulties in using arms
and legs. (blocking of a vessel feeding the arms
and legs with blood)
a. Blocks the blood flow. b. Can travel to other
parts of the body and cause problems.
http//test.cvtcollege.org/Ac_Programs/dms_vascula
r/images/65EABCDF92F4404088B565177BFF8D98.gif
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Why atherosclerosis occurs? Most common polygenic
and environmental factors - Elevated levels of
cholesterol and triglyceride in the blood.
(G/E) - High blood pressure. (G/E) - Tobacco
smoke. (E) - Diabetes. (G/E) - Obesity. (G/E)
The researches has been done on atherosclerosis
suffering individuals and monozygotic and
dizygotic twins.
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http//medlib.med.utah.edu/WebPath/TUTORIAL/DRUG/D
RUG006.html
Two cases of coronary atherosclerosis. Where the
one on the right is more serious than the one on
the left side. Both are cases of atherosclerosis
believed to have been accelerated by smoking.
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... remember blood clotting! Three types of
atherosclerosis I. In the Peripheral vessels
Vessels that feed hands and legs with blood are
blocked. This will finally lead to gangrene in
arms and legs. II. In the Coronaries, (CAD) ?
Heart attack
Most common cause of death in West. E.g. in USA,
CAD is responsible for ca 1.5 million cases of
myocardial infarction (MI), 350,000 cases of
heart failure and 500,000 deaths annually. - WHY?
http//www.racs.edu.au/open/asernip-s.old/publicat
ions_offpump.htm
WARNING FOR THE NEXT TWO SLIDES!!!
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III. In the Carotids. ? Stroke. Vessels that
supply blood to the brain are blocked.
2. Arteriotomy
1. Skin incision
3. Exposure of carotids
4. Removal of atheromatous plaque
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5. Endarterectomy completed-javed shunt being
inserted
6. Arteriotomy closure with a patch
7. Completed closure with a patch
8. Atheroma
http//www.thamburaj.com/surgery_cerebral_ischemia
.htm
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Is atherosclerosis Mendelian or
polygenic? Genetic and environmental. Genetic
Mostly polygenic, but sometimes Mendelian, i.e.
monogenic. Example of monogenic disorders
believed to cause atherosclerosis - Familial
hyperlipidemia (FH). Affected individuals show to
have much higher levels of plasma and LDL
cholesterol, than normal individuals. This causes
CAD. Uncommon disease that affects 1500 in the
population in heterozygous form, and 11,000,000
in the population in the homozygous state. The
responsible gene is the LDL receptor gene
(LDLR). The phenotype of this gene is dependent
on the genetical and environmental factors, diet,
mutation in the modifier gene, etc.
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Mostly polygenic, Very difficult to identify
susceptible genes. - One way is to do the
research based on Mendelian mutations. - We know
that these genes are often involved in biology of
smooth muscle cells, endothelial cells, lipid
metabolism and coagulation. - What do you think?
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Example of two genes believed to play a big role
in triggering coronary atherosclerosis diseases.
Different mutations in these two genes can cause
CAD with different susceptibility.
- ABCA1 gene, This gene codes for ABCA1 protein
that is involved in HDL-C plasma regulation and
apo A1 levels. But in populations the
susceptibility has been shown to be different.
http//www.genomenewsnetwork.org/gnn_images/news_c
ontent/07_01/Trafficking_cholesterol/ABCA1_sm.jpg
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- CYBA gene This gene codes for p22phox protein
that is a component of the plasma
membrane-associated enzyme called NADPH oxidase,
in the vessel walls. CYBA gene is located in
16q24
http//ribosome.miyazaki-med.ac.jp/RPDB/Map/RPL13.
gif
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Summary
-Atherosclerosis is a slow and complex disease
that is hard to discover before diagnosis. - It
is hard to identify a single gene to be
responsible. There are instead genes believed to
be susceptible that with a cooperation with
environmental factors and modifier genes cause
the disease. - Smoking and diet are two major
factors that can cause different types of
atherosclerosis.
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Bibliography
- AMERICAN HEART ASSOCIATION. 2005.
Atherosclerosis. Online. http//www.americanheart.
org/presenter.jhtml?identifier4440. Accessed
March 2005. - HealthAtoZ.com. 2005.
Atherosclerosis. Online. http//www.healthatoz.com
/healthatoz/Atoz/ency/atherosclerosis.jsp.
Accessed March 2005. - HINE R. S. et al. 2004.
Oxford dictionary of biology. 5th edition.
OXFORD. Market House Books Ltd. - SALEK L. AND
MARIAN A. J. 2001. Genetic bases of coronary
atherosclerosis. TEXAS. Baylor college of
medicine. Argentine Federation of Cardiology.