2. Learning Outcomes Identify the components of a lipoprotein.
Describe the role of each of the different lipoproteins
in lipid transport.
Describe the function of an apolipoprotein.
List risk factors for development of atherosclerosis.
Discuss the steps involved in formation of an
atherosclerotic plaque.
2
3. Introduction
Normal blood flow through arteries and veins
requires:
1. an intact system of blood vessels.
2. adequate perfusion pressure to drive the blood
through these vessels.
There are number of diseases that impair the previous
process.
3
4. For the Arteries
Disease-induced changes may impair blood flow
through arteries and disrupt delivery of oxygen and
nutrients to tissues.
4
5. For the Veins
disease processes affecting veins will disrupt removal
of waste products from tissues and the return of blood
to the heart.
5
6. Arterial Diseases 1
Arteries deliver oxygenated blood to the tissues and
organs.
Arteries can vary in size from the large aorta that
transports blood from the heart to medium-sized
arteries that deliver blood to organs and finally down
to small arteries and arterioles that feed blood through
capillary beds
6
7. Arterial Diseases 2
. Arterial diseases include conditions such as
Atherosclerosis.
Aneurysm.
vasospastic conditions.
various inflammatory disorders.
In this lecture we will focus on Atherosclerosis
7
8. Atherosclerosis
Is one of the most common diseases affecting arteries .
It is caused by deposition of lipid plaques in the walls
of arteries.
The formation of atherosclerotic lesions can affect any
artery.
The most commonly affected arteries are the
coronary arteries of the heart.
8
9. Lipid Transport
Because dietary lipids and cholesterol are insoluble in
the plasma, they are transported as part of complex
called a lipoprotein
A lipoprotein is composed of a :
1. hydrophobic core of cholesterol esters and
2. a hydrophilic shell of phospholipids.
9
10. Apolipoprotein
an apolipoprotein is a protein constitutes the protein
portion of the lipoprotein and is responsible for
determining the metabolic fate of the lipoprotein as
well as allowing it to bind to cell surface receptors for
internalization.
10
11. Classification of Lipoprotiens
There are a number of distinct lipoproteins that are
classified according to their density:
1. Chylomicrons
Lowest density
Synthesized in the gut wall
Mainly transport dietary triglycerides from the
intestine into the blood.
11
12. 2. VLDL (very low-density lipoproteins)
Synthesized in the liver
Contains approximately 50% triglycerides with the
remainder approximately equal amounts of
phospholipids and cholesterol
May be converted to IDLs in the blood.
12
13. 3. IDL (intermediate-density lipoproteins)
Composed of approximately equal amounts of
triglycerides, phospholipids and cholesterol Precursor
for LDLs.
13
14. 4. LDL (low-density lipoprotein)
Composed of approximately 50% cholesterol
Main carrier of cholesterol from liver to tissues
Internalized into cells bound to a specific cell-surface
LDL receptor
“Bad cholesterol” due to its role in atherosclerosis.
14
15. 5. HDL (high-density lipoprotein)
Synthesized in the liver
Carries cholesterol from the tissues and plasma back
to the blood
“Good cholesterol” because it removes cholesterol
from the circulation.
high circulating HDL levels associated with a reduced
potential(Risk) for atherosclerosis.
15
16. Formation of atherosclerosis
When serum cholesterol and triglyceride levels are
above normal the condition of hyperlipidemia is
present.
The association between elevated levels of serum
lipids and atherosclerosis has been clearly
demonstrated in a number of studies.
16
17. Normal Range of Cholesterol
The current general consensus in the medical
community is that desirable serum cholesterol levels
are those below 200 mg/dL.
As serum cholesterol levels rise above this range,
there is an exponential increase in the risk of
atherosclerosis and especially disease of the
coronary arteries.
17
18. Causes of Hyperlipidemia
the cause of hyperlipidemia is often multifactorial and
may include poor diet, sedentary lifestyle, or the use
of certain drugs such as β-blockers and oral
contraceptives.
A number of genetic defects may lead to
hyperlipoproteinemia .
Some, such as familial hypercholesterolemia, are
associated with a greatly increased risk for
atherosclerosis and arterial diseases.
18
19. Manifestations of atherosclerosis
Tissue ischemia due to reduced blood flow.
Aneurysm or hemorrhage due to weakening of blood
vessel walls.
Breaking-off of atherosclerotic plaques to form
travelling emboli.
19
20. Risk Factors for Atherosclerosis
A Risk is the probability of occurrence of harm or an
undesirable condition.
Risk factors for atherosclerosis include:
Elevated serum levels of LDL
Low serum levels of HDL
Familial history of hyperlipidemia or atherosclerotic
disease
Smoking
Hypertension
Age > 45 years in males; > 55 years in females
Drugs —β-blockers, oral contraceptives, etc.
20
21. Steps in the Development of Atherosclerosis
1. Formation of lipid plaques may be precipitated by
endothelial injury
(examples: hypertension, immune response, toxins in
cigarette smoke, etc.).
2. Infiltration of cholesterol molecules into blood
vessel walls.
3. Monocytes enter area of injury and release growth
factors that stimulate smooth muscle and
endothelial cell proliferation
21
22. Steps in the Development of Atherosclerosis
4. Monocytes phagocytize lipoproteins and become
lipid-filled “foam cells.”
5. Platelets adhere to the endothelial lesion;
fibroblasts infiltrate area and cause Progressive
sclerosis or hardening of tissue.
5. Calcification of plaques may occur over time.
6. Significant narrowing of the blood vessel lumen can
occur over time.
22