Flashcards in CVM week 10 Deck (39):
Which layer of the artery are the majority of the smooth muscle cells located?
Which layer of the artery are the majority of the fibroblasts, mast cells located?
List some functions of smooth muscle cells?
Normal contractile function, maintain extracellular matrix, contained in the tunica media
List some functions of endothelial cells?
Impermeable to large molecules, anti-inflammatory, resist leukocyte adhesion, promote vasodilation, resist thrombosis
What is atherosclerosis?
Fibrofatty lesions in the intimal lining of large and medium sized arteries. It is a chronic inflammatory response of the arterial wall initiated because of injury to the endothelium. Inside these lesions are lipids, smooth muscle cells as well as connective tissue
What can atherosclerosis lead to?
Progressive narrowing of the arterial lumen which obstructs blood flow- causing ischaemia and promotes thrombus formation
Identify five possible changes that can occur in atherosclerosis to altar the integrity of the blood vessel wall and explain their clinical significance?
1. Narrowing of vessel by fibrous plaque- increased wall rigidity
2. Plaque ulceration or rupture - thrombosis
3. Intrapleural haemorrhage -narrowing of lumen, MI,Stroke
4. Peripheral emboli - fragmentation of plaque , emoticons stroke
5. Weakening of vessel walls- aneurysms
List some non modifiable risk factors of atherosclerosis?
Male sex,age (over 45 in males, over 55 in females), family history.
List some modifiable risk factors for atherosclerosis?
Dyslipidaemia, poor diet (atherogenic), cigarettes smoking, hypertension, diabetes mellitus, metabolic syndrome, obesity, lack of physical activity, thrombogenic state (clotting disorders)
What underlies the disease of atherosclerosis?
Abnormal lipid metabolism
What is correlated with reduced plaque development?
Dietary restrictions and drug therapy to reduce cholesterol levels
What are low density lipoproteins?
They have a role in transporting cholesterol to tissues. High levels of LDL with high cholesterol content are associated with an increased risk of atherosclerosis
What are high-density lipoproteins?
They have a role in transporting cholesterol to the liver for excretion. Low levels of HDL are associated with an increased risk of atherosclerosis.
True or false : elevated high density lipoprotein particles protect against atherosclerosis?
What are the three stages in the pathogenesis of atherosclerosis (brief)?
1.fatty streak formation 2.plaque progression 3.plaque disruption
Which of the stages of the formation of the atherosclerotic plaque are responsible for that clinically significant manifestations of the disease?
Stages 2.plaque progression and 3.plaque disruption
List some factors when in abnormal levels lead to endothelial dysfunction and activation?
Lipoproteins, smoking, cytokines, turbulent flow, oxygen, glucose
What are the changes seen in endothelial cells after inflammatory activation?
Increased: permeability, inflammatories cytokines, leukocyte adhesion molecules
Decreased: vasodilatory molecules, antithrombotic molecules
What are the changes seen in smooth muscle cells after inflammatory activation?
Increased inflammatory cytokines, extracellular matrix synthesis and migration and proliferation into the sub intima
Where do you fatty streaks most commonly occur?
In the aorta and coronary arteries
At what age do most people begin to form fatty streaks in their vessels?
By age 20
What is the most likely cause of fatty streak initiation
How is a fatty streak formed?
LDLs leak into intima. They get trapped and oxidised and then increase expression of leukocyte adhesion molecules onto the endothelial cells. This also causes migration of monocytes to the vessel walls
Does the fatty streak cause any symptoms?
How are foam cell formed?
Monocytes enter into the tunica intima and differentiate into macrophages. The macrophages then engulf/imbibe the modified LDL and evolve into a foam cell
When foam cells die what did they assist in forming?
The necrotic core
what does the accumulation of foam cells in the intima give rise to?
The fatty streak
What do foam cells secrete and what does that assist with?
Secrete proinflammatory cytokines, growth factors, interferon (IFN) q, matrix metalloproteinases (MMP), and reactive oxygen species (ROS) that maintain the chemotactic stimulus for leukocytes adhered to the vascular endothelium, increase the expression of scavenger receptors, enhance macrophage replication and regulate SMC accumulation in the intima
What are scavenger receptors?
Receptors on macrophages that binds preferentially to oxidised LDL causing macrophages to internalise the LDL
Describe stage 2: plaque progression?
Involves smooth muscle migration and proliferation, enhanced lipid accumulation, collagen and other extracellular matrix deposition, lymphocyte infiltration, lipid-rich necrotic core and encapsulation by a fibrous cap
Plaque may progress to form stable or unstable plaque
What is the necrotic core made up of?
Acellular, lipid rich core including cellular debris from foam cells, endothelial cells and smooth muscle cells
What are the predominant factors that affect the stability of an atherosclerotic plaque?
Cell composition and ratio of ECM to lipid content
What would a unstable plaque be like?
Thin fibrous cap, large lipid pool,many inflammatory cells, little collagen, large number of macrophages and a small number of smooth muscle cells
What would a stable plaque be like?
Small lipid pool, thick fibrous cap, preserved lumen
Are stable or unstable plaques more likely to rupture?
List some measures that may stabilise an atherosclerotic plaque?
Decreased LDL, increased HDL, decreased angiotensin II, decreased insulin resistance, decreased oxidative stress, decreased blood pressure
Describe stage 3: plaque disruption ?
Rupture or erosion of the plaques fibrous cap
Where does the rupture most commonly occur in the plaque?
At the shoulder cap of the plaque