L12 - Atherosclerosis Flashcards
What is atheroma?
The accumulation of intracellular and extracellular lipid in the intima of large and medium-sized arteries.
What is atherosclerosis?
The thickening and hardening of arterial walls due to atheroma in large and medium-sized arteries, leading to fibrofatty lesions.
Where does atherosclerosis commonly occur?
• Abdominal aorta.
• Coronary arteries.
• Carotid arteries.
• Cerebral arteries.
• Leg arteries.
How does atherosclerosis develop?
• Starts with endothelial damage.
• Accumulation of lipid, connective tissue, inflammatory cells, and smooth muscle in the intima.
• Progresses from fatty streaks to fibrous plaques and eventually complicated plaques.
What is the response-to-injury hypothesis in atherosclerosis?
• Endothelial dysfunction initiates the process.
• Triggered by LDL, smoking products, immune mechanisms, and mechanical stress.
• Leads to lipid-laden macrophages, foam cell formation, and plaque growth.
What role do LDL and oxidised LDL play in atherosclerosis?
• LDL enters the endothelium and becomes oxidised, altering permeability.
• Oxidised LDL attracts monocytes, forming foam cells and contributing to plaque formation.
• High cholesterol levels increase oxidised LDL accumulation.
What are the types of atherosclerotic plaques?
- Fatty streak: Slight lipid accumulation.
- Simple (fibrous) plaque: Lipid, fibrosis, and smooth muscle migration.
- Complicated plaque: Cap rupture, exposure of plaque contents, and thrombosis.
What are the major cellular events in atherosclerosis?
• Macrophage recruitment and foam cell formation.
• Smooth muscle proliferation and extracellular matrix deposition.
• Formation of a lipid core and cap around the plaque.
What are the non-pharmacological methods to prevent atheroma?
• No smoking.
• Healthy diet (reduce fat, increase fruits/vegetables).
• Moderate alcohol intake.
• Regular exercise and weight control.
What are the pharmacological treatments for atherosclerosis?
• Antiplatelet drugs: Aspirin, clopidogrel, ticagrelor.
• Lipid-lowering drugs: Statins (e.g., atorvastatin, simvastatin).
• Symptom control: Beta-blockers, calcium channel blockers, nitrates.
How does aspirin work as an antiplatelet agent?
• Inhibits cyclooxygenase-1 (COX-1), blocking thromboxane A2 synthesis.
• Irreversible effect lasting for the platelet’s lifespan (7-10 days).
How do clopidogrel and ticagrelor work?
• Clopidogrel: Irreversibly inhibits P2Y12 ADP receptors on platelets.
• Ticagrelor: Reversibly inhibits P2Y12 receptors and is direct-acting.
How do statins reduce cholesterol?
• Inhibit HMG-CoA reductase, reducing hepatic cholesterol synthesis.
• Lower plasma LDL levels, improving lipid profiles.
What are the key learning points about atherosclerosis?
• Affects arteries due to endothelial damage and lipid accumulation.
• Smooth muscle phenotypic modulation leads to plaque growth.
• Antiplatelet drugs block platelet activation and aggregation.
• Statins lower cholesterol production, reducing cardiovascular risk.
