Atherosclerosis 4 Flashcards
What is homocysteine?
A sulphydral containing amino acid produced by demethylation if dietary methionine
What happens when there is a methionine deficiency?
Homocysteine can be re-methylated to form methionine
What happens when there is sufficient methionine?
Homocysteine is used to produce cysteine
What enzyme converts homocysteine to cystathionine then cysteine?
Cystathionine-β-synthase
What is homocysteine described as?
An independent risk factor for atherosclerosis
What are mutations in Cystathionine-β-synthase associated with?
Excess levels of homocysteine and premature thrombotic events
Bitamin B6, B12 and folic acid reduce or increase serum homocysteine levels?
Reduce
What are matrix metalloproteinases?
Zinc-dependent endopeptidases
What do matrix metalloproteinases do?
Degrade components of the extracellular matrix and basement membrane
What is plaque erosion?
Focal areas of endothelium become denuded and expose underlying connective tissue
What is plaque rupture?
A structural defect in the fibrous cap that separates the necrotic lipid core of an atherosclerotic plaque from the lumen, resulting in exposure of the necrotic core to the blood via the gap in the cap
What are the signs of plaque rupture?
Intra-plaque haemorrhage, fracture cap fibres and multilayered buried caps
What do plaques that rupture tend to have?
Large necrotic cores, thin collagen caps, increased inflammatory cell activity and increased amounts of proteolytic enzymes
What do plaques that erode tend to have?
Smaller necrotic core, less immune cells but containing proliferating smooth muscle cells and display neovascularisation
What receptor is involved in platelet activation?
Adenosine nucleotide GPCRs (P2Y receptors)
Why do LDL cholesterol bind to platelet receptors?
To regulate activity
What is CD36?
Class B scavenger receptor that binds oxidised LDL, collagen and thrombospodin
Oxidised LDL is a potent platelet activator which leads to what?
intraplatelet reactive oxygen species formation via assembly and formation of NADH oxidase activation.
Increase in ROS activates what?
MAPK signalling pathways sensitive to cellular oxidative stress
P2Y12 receptor is the target of what?
Antithrombotic drugs e.g clopidogrel
What are clopidogrel and prasugrel?
Irreversible P2Y12 antagonists
What is cangrelor?
Oral agent and a reversible P2Y12 antagonist
