Atherosclerosis Flashcards
What arteries are affected by atherosclerosis?
Large and medium-sized arteries.
What are atheroslcerotic lesions made up from?
Fatty streaks, fibrolipid plaque and complicated (thrombosed) lesions.
What are the risk factors for atherosclerosis?
Increasing age
Male gender
Hypertension
Smoking
Diabetes
What molecules are associated with atherosclerosis?
Increased LDL
Lp(a)
Fibrinogen
Factor VII
Reduced HDL
What is a major consequence of atherosclerosis?
Organ ischaemia
Atherosclerosis is characterised by
Formation of focal elevated lesions in the intima of vessels.
What causes life threatening damage?
Occlusive thrombosis forms on a spontaneously disrupted plaque (known as atherothrombosis).
What is a fatty streak?
Earliest significant lesion - yellow linear elevation of the intimal lining. Composed of masses of lipid-laden macrophages. Can develop to plaques.
Describe a fully developed plaque.
A lesion with a central lipid core + fibrous cap covered by arterial endothelium.
What is the fibrous cap made up from and what produces this?
Collagen and is made by the smooth muscle cells.
What other cell types are found in the fibrous cap?
Macrophages, T-lymphocytes and mast cells.
Describe atheromatous lesions.
Rich in cellular lipids and debris.
They are soft, semi-fluid, thrombogenic lesions bordered by foam cells.
What are foam cells?
Macrophages that phagocytosed oxidised lipoproteins via special membrane bound scavenger receptors. They have large amounts of cytoplasm with a foamy appearance.
Where are plaques most likely to form?
At arterial branching points and bifurcations.
What is the most important risk factor?
Hypercholesterolaemia.
Plasma cholesterol levels>8 mmol/L
What are the less strong risk factors?
Obesity sedentary lifestyle, low socio-economic status and low birth weight. Recurrent infections with pathogens such as dental pathogens are thought to increase the risk as well. (switching on inflammatory pathways.
What are the two steps in the development of atherosclerosis?
- Injury to the endothelium.
- Tissue response to the injury.
Describe the pathogenesis of plaque formation.
Injury to endothelial cells - increased expression of ICAM-1 (adhesion for monocytes) and E-selectin (high permeability for LDL) and increased thrombogenicity.
Inflammatory cells and lipids enter the intimal layers.
In more advanced stages large amounts of macrophages and T-cells.
Foam cells die via apoptosis - releasing lipids.
Describe the steps of tissue repair in lesion formation.
The inflammatory reaction is followed by PDGFs stimulate intimal SMCs -> collagen synthesis, elastin and mucopolysacharride synth.
Fibrous cap encloses the lipid-core.
What secretes GFs?
Platelets, injured endothelium, macrophages and SMCs.
What is another important mechanism of plaque growth?
Haemorrhage. Rupture or leakage of microvessels within plaque.
What are the clinical manifestations?
- Progressive lumen narrowing due to a high grade plaque stenosis. 50-75% occlusion - reversible.
Stable angina (stenosed coronary artery)
Intermittent claudication (iliac/femoral/popliteal artery).
- Acute atherothrombotic occlusion= plaque rupture= high thrombogenic components exposed.
Total occlusion leads to necrosis.
- Embolism= detachment of small thrombus fragment.
In carotids= cause of stroke - Ruptured AAA= retroperitoneal haemorrhage and death.
The vulnerable plaque concept
High risk of developing thrombotic complications.
Thin fibrous cap, large lipid core and inflammation due to proteolytic enzymes, CKs, ROS.
Preventative and therapeutic approaches.
- Smoking cessation
- BP control
- Weight reduction
- Regular exercise
- Dietary modifications
- Statins (inhibit HMG CoA reductase enzyme (rate limiting in hepatic cholesterol synthesis).
- Low dose of aspirin inhibits platelet aggregation.
Surgical:
- Endarterectomy intima is cored out from the underlying media.
- Percutaneous angioplasty crack open atheromatous plaques by using an inflatable balloon.
- Bypass - saphenous vein or fabric grafts
