Dyslipidemia - Intro Flashcards
How does an atheroma form?
a lesion/fatty streak forms
- appear when foam cells present at the site of plaque formation expand
an accumulation of smooth muscle cells - form over the lipids expansion of foam cells - ingest LDLs fibrous cap forms over the smooth muscle cells and lipids - prevents exposure of lipids
thrombus forms
- forms as plaque ruptures causing the exposure of cholesterol and tissues that were under the fibrous cap
= blood cells are attracted and platelet activators adhere
What is an atheroma?
build up of materials that adhere to the artery walls
- cholesterol, fats, inflammatory cells
causes atherosclerosis
- disease where the arteries narrow due to build up of plaque
What are the modifiable risk factors of cardiovascular events?
hypertension and dyslipidemia
- reducing/treating these conditions can reduce the risk of cardiovascular events
= heart attack, stroke and ischaemic heart disease
What are LDLs, HDLs and triglycerides?
LDLs - low density lipoproteins
HDLs - high density lipoprotein
increased levels of LDLs and triglycerides increase the risk of cardiovascular events
What are lipoproteins?
are proteins found in the bloodstream which transport cholesterol and triglycerides through the bloodstream
What is the difference between
- LDLs, HDLs, chylomicrons, vLDLs and IDLs?
size, density and proportions
chylomicrons, vLDLs, LDLs, IDLs and HDLs
lowest density to highest density
biggest size to smallest size
as the size of lipoproteins increases, the density decreases
HDLs have less cholesterol and triglycerides than LDLs
What are apoproteins?
molecules attached to the membrane of the lipoprotein coat
- allows detection of lipoproteins by cells
= enables uptake into cells
What is an endogenous source? How are they synthesised?
endogenous sources of cholesterol are those within the body
- made in the liver and secreted in vLDL
main sources are glycogen (glycogenolysis/glycolysis), triglycerides (lipolysis) and proteins (proteolysis)
- after a series of reaction, they form acetyl-CoA which is a precursor to cholesterol
What is an exogenous source? Where do they come from?
an exogenous source of cholesterol comes from outside the body
- are consumed
= triglycerides and cholesterol
are absorbed from the intestine as chylomicrons (largest lipoprotein)
What is the purpose of lipoprotein lipase?
enzymes which remove triglycerides
- break down triglycerides so it can be taken up into tissues for storage or used for energy
How is cholesterol formed from acetyl-CoA?
HMG-CoA synthase is the enzyme which begins the reaction
HMG-CoA reductase = enzyme
- is the rate limiting step
= controls the amount of cholesterol production
How is cholesterol trafficked around the body?
cholesterol leaves the liver in vLDLs and circulates the body in the bloodstream
lipoproteins are broken off cholesterol via the action of enzyme lipoprotein lipase
- forms smaller and denser LDLs
LDLs traffic cholesterol to tissues
- can lead to accumulation of cholesterol in blood vessels
HDLs traffic excess cholesterol to the liver where it can be removed via excretion as bile
cholesterol can be absorbed across the intestine to enter the blood in chylomicrons
How do LDL receptors work?
LDL binds to LDL receptors on cells
the LDL-LDL receptor complex is endocytosed
- forms a clatherin coated vesicle
LDL is removed and is contained within an endosome (membrane bound vesicle)
LDL is recycled back up to the membrane
What is familial hypercholesterolaemia? What causes it? What is its effects?
mutations in LDL receptors and protein PCSK9 are associated with familial cholesterolaemia
- is a genetic disorder and is hereditary
PCSK binds to the LDL receptor
when the LDL comes and binds to the PCSK-LDLr complex, it is endocytosed
PCSK9 results in receptor degradation
- are broken down by lysosomes
= reduces the number of LDL receptors on the cell surfaces resulting in LDL build up in the blood
What are PCSK9 proteins?
proteins which cause the degradation of LDL receptors when they are endocytosed
high levels of PCSK9 are biomarkers for cardiovascular risk
