Lipoproteins as risk factors for heart disease Flashcards
What does LDL have a high affinity for?
And where is it made?
The arterial wall, where they are uptaken by macrophages to form foam cells.
Made in the liver.
LDLs function is to transport cholesterol from the liver to peripheral tissues, whereas HDL transports peripheral cholesterol to the liver.
Descibe how foam cells are made
LDL has a high affinity for the arterial wall.
It binds to alot of structures e.g. collagen & elastin, proteoglycans (mainly through apoB found on the surface of LDL) which interacts with those proteins.
Once in the arterial wall the lipids gets oxidised, and oxidised lipids act as an inflammatory signal to stimulate surround cells in the artery wall.
Involved in the inflammatory response are cell adhesion molecules, they bring in WBCs into the arterial wall. So monocytes get attracted, they bind to the cell adhesions. They then migrate into the arterial wall, then differentiate into macrophages and express scavenger receptors which take up the oxidised LDL to form foam cells
How can foam cells be seen grossly?
As fatty streaks
What are the atherogenic properties of LDL?
It’s has a high affinity for the arterial wall
Lipids within are easily oxidised (then taken up by macrophages)
Oxidised LDL promotes inflammation
Oxidised LDL promotes thrombosis (since it promotes platelet aggregation
How can LDL be lowered?
- Diet
- Lipid lowering drugs (statins)
- Weight loss
- Exercise (lowers LDL, increases HDL)
What is Lp(a)?
And how does it contribute to arthrogenesis?
It’s a cholesterol rich lipoprotein. It’s a modified form of LDL in which the apo-B is disulphide linked to apo(a), a glycoprotein highly homologous to plasminogen.
The more kringle 4 domains there are on apo(a), the larger the protein.
However there is an inverse correlation between the number of apo(a) kringles and the conc. of the Lp(a). The lower the number of kringles on apo(a), the higher the concentration of Lp(a)
- Addsd to lipid accumulation in the blood vessel wall
- Blocks the activation of plasmin by competing with plasminogen for binding to fibrin and therefore interfering with the lysis of blood clots.
- Stimulating smooth muscle cell proliferation
What determines ones Lp(a) levels?
It’s entriely genetic
Where is HDL made, and how does it pick up cholesterol?
synthesised in the liver, and binds to ABCA1 via its ApoA-1 apolipoprotein to pick cholesterol up.
What are the causes of low HDL?
Low HDL is usually due to defects to ApoA-1, or ABCA1
- Liver disease
- Genetics
- Secondary to altered lipoprotein metabolism
- Familial combined hyperlipidaemia
- Type 2 diabetes mellitus
- metabolic syndrome
What are the protective effects of HDL on atherogenesis?
HDL has both antioxidant and anti-inflammatory properties.
Antioxidant and anti-inflammatory properties: Prevents LDL being oxidised, and therefore it prevents inflammation from occuring, and prevents monocytes from being attracted and binding to cell adhesions, and this from becoming scavenger cells and thus foam cells.
The HDL gets trough the arterial wall and interact with ABCA1, and then escape back into the blood stream after getting the choelsterol.
What are the protective mechanisms displayed by HDL?
- Removes cholesterol from the arterial wall
- Antioxidant properties
- Anti-inflammatory properties
- Anti-thrombogenic
What can be done to increase HDL?
- Lipid lowering drugs (statins,fibrates,niacin)
- Weight loss
- Exercise
- Alcohol ??
- Diet (saturated fat) ??
- CETP inhibitors?
- ApoA1 mimetic peptides?
What happens in Hypoalphalipoproteinemia? (Low HDL)
- Quite common
- Reduced plasma HDL
- Premature heart disease
- Due to mutations in the ABCA1 cholesterol transporter (heterozygous form) which reduce cholesterol efflux from cells
- Approx. 10% of low HDL individuals have ABCA1 mutations
