CVS 16 - Atherosclerosis Flashcards
What are some risk factors for atherosclerosis?
- Smoking
- Lipids
- BP
- Obesity
- Diabetes
- Age
- Sex
- Genetics
Having multiple risk factors causes the risk to be multiplicated
Why do atherosclerotic plaques tend to form on outside of the bend rather than the inside?
When blood flows around a corner too quickly it forms an EDDY (turbulent flow).
This causes atherosclerotic lesions to appear on the outside of bend rather than the middle
Where do LDLs bind to form atherosclerotic plaques?
In the suboptimal space and binds to matrix proteoglycans.
Explain how an atherosclerotic plaque progresses
- LDLs enter subintimal layer.
- LDL accumulation brings in macrophages - these eat up endothelial fat and the macrophages become foam cells.
- Fat deposition continues - lesion accumulates pools of extracellular lipid (outside macrophages). Macrophages can no longer cope.
- Further fat buildup causes extracellular lipid core - fatty coalescence causes large fatty mass.
- Inflammation causes irritation in the interior of the plaque - which causes a fibrous thickening.
- Macrophages produce growth factors - stimulate SMC to grow and divide - making more collagen.
- Plaque eventually ruptures - lipid core can then stimulate clot formation in the lumen.
Describe the layering effect
Repeat episodes of plaque destabilisation. Small episodes of thrombus formation then stopping. The thrombi form one after another - lumen narrowed a little at a time.
What are the 5 main cell types and their roles, in relation to atherosclerosis?
- Vascular endothelial cells - barrier function and WBC recruitment
- Platelets - thrombus generation, cytokine and GF release
- Monocytes/macrophages - foam cell formation, cytokine/GF release, source of free radicals, metalloproteinases
- VSMC - Migration and proliferation, collagen synthesis, remodelling and fibrous cap formation
- T cells - macrophage activation
What are foam cells?
Macrophages that have consumed fat
What do matrix metalloproteinases do?
Degrade major EC proteins e.g collagen
What are the main inflammatory cells in atherosclerosis?
Macrophages
There are 2 main types of macrophages, and their formation is regulated by TFs binding to regulatory DNA sequences. What are the 2 classes?
- Resident - mainly homeostatic (suppress inflammatory activity, alveolar resident macrophages, osteoclasts, spleen)
- Inflammatory - kill microorganisms
Describe 3 types of lipoprotein.
- LDL - synthesised in liver. Carries cholesterol from liver to rest of body
- HDL - carries cholesterol from peripheral tissues back to liver
- Oxidised LDL/Modified LDL - caused by free radical action. Not one single substance - family of high inflammatory/toxic forms of LDL in vessel walls.
Describe LDL structure.
- Consist of lipid monolayer
2. Has apoproteins on outside telling it were to go
LDLs can leak through the endothelial layer. What happens if they leak?
They are trapped in the sub endothelial layer by sticking to sticky matrix carbohydrates.
How are the sub endothelial trapped LDLs modified?
- Free radicals oxidatively modify the LDLs.
2. Oxidised LDL is phagocytosed by macrophages, forming foam cells. This stimulates chronic inflammation.
What is familial hyperlipidaemia and what implication does it have?
Autosomal recessive genetic disease - causes massively elevated cholesterol levels (20mmol/L).
Failure to clear LDL from blood causes xanthomas (accumulations of foam cells).
May result in fatal MI by the age of 20.