Atherosclerosis Flashcards
Atherosclerosis
Disease affecting the innermost layer of large and medium sized arteries. Appears as focal thickenings called ‘plaques’, which are deposits of fibrous tissues and lipids.
Thought to contribute to 50% of deaths in the western world
What layer of the endothelium wall is affected in atherosclerosis
The Tunica intima.
Contains
-endothelial cells(in contract w intra-vascular cells): involved in BP and inflammation, separated by tight junctions,
- Scattered myointimal cells
- BM: presents growth factors, anchors cells, with a IEL
Tunica Media of arteries
an EEL and smooth muscle cells
SM: regulates flow by contraction, and stabilise EC by secreting ECM and activating TGF-beta
What do the Elastic Lamina Layers look like in a histology section?
Pink and wavy
Tunica Adventitia of the arteries
Connective Tissue: fibroblasts, nerves, leucocytes, lymphatics, blood vessels (vasovasora)
How is the exact structure of arteries dependent on their size?
Large arteries > exposed to high-pulsitile pressures > have prominent elastic laminae and are called “elastic arteries”
Medium Sized arteries > media largely composed of SM cells > “muscular arteries
Muscular arteries
eg) coronary arteries
- Media largely composed of SM fibres
- Few elastic fibres
- Separate Int/Ext elastic Laminae
Large elastic arteries
eg) Aorta, common carotid
- Media contains prominent elastic laminae
- Int/Ext Elastic laminae continuous
- Exposed to high pulsitile pressure
- Elastic recoil assist w continuous flow
Arterioles
Small branches within tissues
Clinically risk factors ____ and are therefore _______
Clinically risk factors synergise and are therefore considered together
Main Positive Risk Factors of Atheroscelorsis (increase disease risk)
- Hyperlipidaemia: (inc lipids in blood, especially cholesterol)
- Cigarette smoking
- Hypertension
- Diabetes mellitus
**advancing age
Additional + risk factors of Atheroscelrosis
Family history (polygenic inheritance) Male High sat-fat diet Stressful & sedentary lifestyle Obesity & metabolic syndromes Excess alcohol consumption Low birth weight Low Socioeconomic status Infections
What is a risk factor that can be BOTH + and -??
A little alcohol is +
A lot of alcohol is -
Theory is alcohol has some antioxidants
Negative Risk factors for Atherosclerosis (decrease risk)
High levels of HDL
Moderate alcohol consumption
Cardiovascular fitness
Lipoproteins as powerful risk modifiers for Atherosclerosis
Lipoproteins: lipid core, surrounded by a protein coat (apolipoproteins)
Abnormal blood levels of lipoproteins may alter atherosclerosis risk.
-Cholesterol greatly increases risk
whereas
HDL > decreased risk
LDL > increased risk
Whats the pathogenesis of Atherosclerosis
Several theories, but the precise process in uncertain.
Initiation: may involve endothelial cell injury
Progression: is an example of chronic inflammation
1) Endothelial cell injury
2) Leukocyte Migration
3) Smooth Muscle activation and migration
4) Lipoprotein infiltration
Endothelial cell injury. Caused by?
Thought to be one of the most important initiators of atherosclerosis
Caused by a combo of injuries or stresses: haemodynamic force of blood(hypertension), chemical insults (smoking, lipids), cytokines
Caused most predominantly at BV junctions
Endothelial cell injury may lead to…
- Altered permeability (lipid infiltration)
- Adhesion and activation of leucocytes (due to enhance expression of chemokines and adhesion molecule)
- Activation of thrombosis (turn on blood clot formation)
- In addition endothelial progenitors are recruited
Gradually plaque begins to build up under endothelial cells
Leukocyte Migration into the developing plaque
Type of chronic inflammation
1) Circulating monocytes adhere to endothelial cells and enter the atherosclerotic lesion
2) They then differentiate into macrophages
3) Once in the plaque, they ingest large amounts of oxidised lipoproteins which give them a foamy appearance > “foam cells”
4) When they die by necrosis (or apoptosism), their contents including lipoproteins, spill into the extracellular space. (potent activation of inflamm)
Smooth muscle cell activation and migration
1) macrophages, platelets and endothelial cells produce growth factors that activate vascular smooth muscle cells
2) Once activated, SM cells proliferate and migrate into the tunica intima from the tunica media
* *accelerated by failure of the IEL
Activated SM:
produces cyto/chemo kines that activated leukocytes
take up lipids
produce ECM proteins
Lipoprotein infiltration and oxidation
LP’s become oxidised in plaques. When Endothelial cell is damaged LDL can infiltrate, and is a risk of oxidisation by ROS.
Oxidised lipoproteins:
-attract monocytes > macrophages which injest LDL and form foam cells, as they cannot breakdown the LDL
-stimulate several cell types to release cytokines, inflamm mediators and ROS, growth factors
These cause more dysfunction, inflammation and apoptosis in smooth muscle cells, macrophages and endothelial cells. A viscous cycle
***IEL may be a protective barrier
Draw an atheroma lesion
….
Pre-clinical to clinical phase of atherosclerosis
Silent phase,
Normal artery progression to an advanced plaque UNTIL they suddenly cause symptoms due to rupture, haemorrhage, thrombosis or dissection.
Clinical consequences of atherosclerosis
Myocardial infarction
Peripheral vascular disease
Cerebrovascular disease (strokes)