Atherosclerosis Flashcards
Describe the three layers of the arterial wall
Tunica intima- endothelial cells lying on a basement membrane. Include the internal elastic lamina.
Tunica media- smooth muscle cells includes external elastic lamina
Tunica externa- connective tissue includes fibroblasts, leucocytes, lymphatics, vast vasorum, nerves.
Main risk factors for atherosclerosis
Hyperlipidaemia
Smoking
Hypertension
Diabetes mellitus
Additional risk factors
Age Family hx Male Stress Sedentary lifestlye Obesity Excess alcohol Low SES Infections (chlamydia)
Negative risk factors for atherosclerosis
High HDL levels (these lipoproteins carry the cholesterol away from the vessel wall)
Cardiovascular fitness
Moderate alcohol intake
Define lipoprotein
A soluble protein that transports lipids in the serum.
What are the proposed causes of endothelial cell injury in atherosclerosis
- Haemodynamic force of the blood (hypertension)
- Chemical insults (cigarette smoke)
- Cytokines (inflammation)
What may endothelial cell damage in atherosclerosis lead to
Altered permeability (lipid infiltration)
Adhesion of leucocytes (chemokines/ adhesion molecule expression)
Activation of thrombosis
List the key changes that occur in the vessel wall in atherosclerosis
Endothelial cell injury
Leukocyte migration
Smooth muscle cell activation and migration
Lipoprotein infiltration
Describe leukocyte migration in atherosclerosis
Neutrophils- maybe involved initially but seen in mature plaques
Monocytes- adhere to endothelial cells and enter atherosclerotic lesion and mature to macrophages. Here they take up oxidised lipoproteins and become foam cells (due to foamy appearance). They die in the plaque and contribute to the necrotic core, cholesterol crystals and calcification.
Mast cells- degrade protective HDL and promote smooth muscle and leukocyte migration into the plaque
Describe the smooth muscle cell activation and migrations effect in athersclerosis
Macrophages, platelets and endothelial cells produce growth factors that activate smooth muscle cells. Once activated they proliferate and migrate into the tunica intimate from the media.
They produce cytokines and chemokines that activate leukocytes, and take up lipids
Describe lipoprotein infiltration in atherosclerosis
Lipoproteins become oxidised in plaques. Then they attract monocytes, and stimulate several cell types to release cytokines, growth factors. Cause dysfunction in smooth muscle cells, macrophages, and endothelial cells.