By Dr Mustafa Awadelkareem

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.

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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.

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For the Arteries Disease-induced changes may impair blood flow

through arteries and disrupt delivery of oxygen and nutrients to tissues.

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For the Veins disease processes affecting veins will disrupt removal

of waste products from tissues and the return of blood to the heart.

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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

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Arterial Diseases 2 . Arterial diseases include conditions such as

Atherosclerosis.

Aneurysm.

vasospastic conditions.

various inflammatory disorders.

In this lecture we will focus on Atherosclerosis

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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.

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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.

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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.

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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.

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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.

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3. IDL (intermediate-density lipoproteins)

Composed of approximately equal amounts of

triglycerides, phospholipids and cholesterol Precursor for LDLs.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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Thank you

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