atherosclerosis Flashcards
(30 cards)
LCAT (lecithin cholesterol acyltransferase)
- converts cholesterol into cholesterol esters
- activated by Apo A
- important for reverse cholesterol transport (HDL formation)
LPL (lipoprotein lipase)
- hydrolyze the TG in CM and VLDL to glycerol and FFA
- allow delivery of TG to peripheral tissue
- activated by Apo C
HL (hepatic lipase)
- hydrolyze TG to glycerol and FFA from CMR in liver
- key way for liver to extract TG from lipoproteins
- VLDL and IDL metabolism in liver
ABCA1
- a cholesterol efflux protein
- transfers free cholesterol out of the cell for HDL formation in reverse cholesterol transfer
LDL receptor
binds to LDL and facilitates endocytosis
- dysfunction of absence of LDL receptor leads to familial hypercholesterolemia
HMG- CoA reductase
rate limiting step in de novo cholesterol syntesis (most cholesterol is produced in liver, not from diet)
- feedback inhibited by cholesterol
Cholesterol- 7-alpha-hydroxylase
rate limiting step in bile acid synthesis
- stimulated by cholesterol
- suppressed by bile acids
Chylomicrons
transport dietary TG and cholesterol from intestine to tissues
VLDL
transport TG from liver to tissues
IDL
remnant of VLDL that is converted to LDL
LDL
deliver cholesterol to peripheral tissues
HDL
reverse cholesterol transport
- delivers cholesterol to liver from peripheral cells via SR-B on liver
- shuttles Apo C and Apo E
drugs to treat low HDL
Fibrate
drugs to treat high LDL
statin & bile acid sequestrins (BAS)
How does Fibrate work?
promotes HDL formation by activating PPAR receptor and LXR/RXR receptors–> promotes ABCA1 expression in cell membrane–> increases cholesterol effluxed –> promotes reverse cholesterol transport and HDL formation
How does Statin work?
blocks de novo cholesterol production by:
statin decreases intracellular cholesterol –> removes suppression of LDL receptor –> receptor is free to move to plasma membrane surface –> LDL receptor on surface clears more plasma cholesterol
how does BAS work?
BAS binds to bile acid in the intestine so it is secreted in feces–> enterohepatic recycling of bile acid no longer occurs –> intracellular cholesterol is recruited for bile acid synthesis –> frees up LDL receptor in intracellular space –> LDL receptor is free to move to plasma membrane surface –> LDL receptor on surface clears more plasma cholesterol
Anti-inflammatory properties of HDL (3)
- reverse cholesterol transport to remove cholesterol esters from foam cells
- inhibit adhesion molecule expression by endothelial cells
- reduce oxidation of LDL particles in intima
Pathways of homeostasis in Liver (4)
- disposal via bile acid synthesis (7-alpha-hydroxylase)
- storage of cholesterol as cholesterol esters (ACAT)
- de novo synthesis of cholesterol (HMG-CoA reductase)
- endocytosis of LDL (LDL receptor)
MCP-1
- expressed in endothelial cells
- activated by oxidized LDL and causes recruitment of monocytes from the blood
foam cell
lipid laden macrophage
fibrous cap
combo of lipid laden foam cells and extracellular matrix of smooth muscle cell that forms on vascular wall to cause atherosclerosis
if low HDL where do you worry that cholesterol is being stored?
peripheral tissues
Apo A
- stimulates LCAT to convert free cholesterol to cholesterol esters
- required for HDL formation
