Atherogenesis

Atherogenesis

When inflammation occurs inside an artery and fatty streaks, fibrous plaques, and clots are formed

athero/arteriosclerosis

Atherogenesis leads to:

Arteriosclerosis

Abnormal thickening and hardening of vessel walls. Smooth muscle and collagen fibers igrate into tunica intima, stifen and thicken, and narrow the arterial lumen

Atherosclerosis

Form of arteriosclerosis caused by soft deposits of intra-arterial fat and fibrin that harden overtime, leading to vessel narrowing

1. HTN

2. IHD

3. MI
   peripheral vascular disease

4. cerebrovascular disease

Atherogenesis associated diseases [5]

An inflammatory response to endothelial damage. where repair, the end stage of inflammation, causes a defect in the arterial wall

Atherogenesis is a response to what?

1. damaged endothelium

2. fatty streak

3. fibrous plaque

4. complicated lesion

Stages of atherogenesis: [4]

LDLs

When the endothelium is damaged, what moves into the intima?

platelets aggrefate on the exposed subendothelium and stimulates formation of a platelet plug, serotonin is released.

When the endothelium is damaged, what happens with platelets?

serotinin causes an increase in vascular permeability and monocytes migrate to site and mature into macrophages.

What does serotonin do in vessels when released from platelets in platelet plug?

They move into the intima of the vessel wall with the LDLs that are there. Once inside, they will engulf LDLs/

What do macrophages do once they have matured in subendothelium?

Lipid oxidation

When macrophages engulf LDLs but they are not destroyed, instead they form foam cells

Fatty streak

When lipid-filled foam cells aggregate, they form WHAT in the vessel intima?

1. Releasing grwth factor so smooth muscle cells move from media to intima

2. secretes cytokines

At the same time they are engulfing LDLs (lipid oxidation) what else are macrophages doing?

They proliferate in the intima, that migrate over the fatty streak

when macrophages stimulate growth factor, what happens to smooth muscle cells in the intima?

This stimulates fibroblasts to multiply, and they migrate to the intima and produce collagen. this migrates over the fatty streak

When macrophages secrete cytokines, what happens in the intima?

Fibrous plaque

When smooth muscle cells and collagen migrate over the fatty stream, this forms a:

1. physical build up of plaque can lead to obstruction

2. can become a complicated lesion

results of fibrous plaque formation

Narrows blood vessels so increasing PVR.

how do fibrous plaques lead to HTN?

1. angina

2. intermittend claudicaition

3. transient ischemic attack (TIA)

Plaque formation can lead to ischemia, causing: [3]

As the plque breaks through the surface of the endothelium, it is rough and passing platelets stick to it.

how can plaques become a complicated lesion?

Thrombus

Platelets sticking to a fibrous plaque can lead to formation of a:

1. when platelets adhere to the plaque, they actiate and aggregate

2. they release serotonin

3. serotonin can cause transient vasocontriction

4. leads to vasospasm (ischemia)

How can a thrombus lead to instant ischemia:

1. platelet aggregation continues

2. forms a blood clot (thrombus)

3. occludes the vessel

4. leads to ischemia/infarction

How can a thrombus (occlusion) form with a fibrous plaque?

hypoxia due to inadequate perfusion of itssues

clinical manifestations of thrombus formation arise from:

partial vessel obstruction that leads to transient ischemic events, often associated with exercise/stress

early thrombus formation symptoms come from:

Complicated lesions leading to increased obstruction and tissue infarction

Later thrombus formation clinical manifestations come from:

1. sex

2. family history

non modifiable risk factors for atherosclerosis [2]

1. LDL/HDL levels

2. microclots

3. injurous stimuli (smoking, HTN, poorly controlled diabetes or metabolic syndrome)

modifiable risk factors for atherosclerosis: [3]

1. triglycerides

2. cholesterol

lipoproteins transport:

energy and membrae syntehsis

triglycerides are necessary for:

hormone synthesis

cholesterol is necessary for:

1. triglycerides

2. cholesterol

3. proteins

Lipoproteins consist of: [3]

the more protein. Proteins weigh more than lipids.

the higher density the lipoprotin, the:

VLDL (bad!)

lipoprotein with a high lipid:protein ratio

LDL (bad!)

still bad lipoprotein but less lipid than VLDL

Transports lipids from adipose tissue to peripheral tissue

function of LDLs

2.6 mmol/L

LDL should be less than:

Carries lipids away from peripheral tissue to liver for degradation

HDL function:

HDL (GOOD!)

lipoprotein with less lipid than LDL

1. 0.91-1.68 or greater for men

2. 0.91-2.07 or greater for women

HDL levels should be:

because LDLs transport lipids from adipose tissue to periphery

and HDLs carry lipids away from periphery to the liver for degradation

Why is higher lipid content in lipoproteins worse?

Has high lipid content, carried to tissues where it can be oxidized to form foam cells and sued in plaque formation

Why is increased LDL a risk factor for atherosclerosis?

Has a high protein content, carries lipids to liver and therefore reducing plaque formation

Why is increased HDL a protective function against atherosclerosis?

1. glycosylated basement membranes can be perceived as endothelial injury (stage 1 of atherogenesis)

2. Elevated VLDL/LDL levels due to high triglycerides

how can poorly controlled diabetes by a risk factor for atherosclerosis? [2]

contributes to endothelial injury because there is turbulent blood flow (stage 1 atherogenesis)

how can HTN be a risk factor for atherosclerosis?

1. stimulates the release of catecholamines so…

2. Increase HR, FOC, and PVR, so increase BP and workload

3. stimulates release of fatty acids

4. many chemicals ca damage endothelium.

how can smoking be a risk factor for HTN?

Associated with higher HDL levels so more foam cells are formed

How is a high fat diet a risk factor for atherosclerosis?

Is associated with high LDL because less exercise and you burn less LDL for energy.

How is asedentary lifestyle a risk factor for atherosclerosis?

increases triglyceride levels and BP

how is heavy alcohol use a risk factor for atherosclerosis?

it increases HDLs!!

How can moderate use of alcohol DECREASE risk fo athersclerosis?

more anxiety and chronic stress so

1. more catecholamines leads to HTN (increased HR, FOC, PVR)

2. increased cortisol (more fatty acids available)

why is a type A personality a risk fo atherosclerosis? [2]

they have less estrogen

Why do men have higher risk of developing atherosclerosis?

estrogen levels drop

Why do post-menopausal women have increased risk of atherosclerosis?

Decreases LDL and increases HDL (GOOD)

affect of estrogen on lipoproteins:

1. reduction of dietary saturated fats

2. control of glucose levels

how can LDLs be reduced? [2]

With exercise. Lipids in LDL/VDLDL are used for energy so you are left with HDLs.

How can HDLs be increased?