Lecture 9 - ATHEROSCLEROSIS AND DYSLIPIDEMIAS Flashcards
Lipid transport throughout the body is mediated by 3 lipoprotein complexes:
- HDL (high density lipoprotein)
- LDL (low density lipoprotein)
- VLDL (very low density lipoprotein
``
Lipids are ____ in blood or water; they travel around the lipoproteins.
not soluble
High level of total ____ are linked to adverse cardiovascular events which is attributed to the formation of atheroscleorotic plaques.
cholesterol
What is the leading cause of death in North America?
Rupture of atherosclerotic plaques followed by occlusion of vessels in the heart or brain
What is Artherosclerosis?
Fatty deposits that occlude blood vessels and form plaques overtime as cholesterol accumulates.
Accumulation of cholesterol occurs over time in transformed macrophages also known as ____ cells that have invaded the ________ of a blood vessel.
FOAM; endothelial wall
- Is high LDL a good thing?
- Is high HDL a good thing?
- High LDL is a bad thing as it means that you are delivering/adding more cholesterol to plaques
- High HDL is a good thing as it means you are taking cholesterol away from the plaque.
What prodrugs are effective in controlling cholesterol content in the body?
Statins
Where is VLDL and LDL regulated in the body?
regulated in the liver.
Where is cholesterol formed?
liver
LDL circulating around the body can be taken up by ____ cells and by ____ cells by LDL receptors.
peripheral;liver
Cholesterol that is packaged can be dietary/____ (taken up via the ____ receptor) or synthesized in the ____ ____
extrinsic; LDL; liver hepatocyte.
What key enzyme is involved in the formation of cholesterol?
HMG-CoA reductase
What is the effect on cholesterol if HMG-CoA reductase is inhibited?
reduction in the amount of cholesterol produced by the liver; leads to an increased expression of LDL receptors on the hepatocyte.
HMG-CoA is a ____ protein, primarily residing in the ER membrane.
transmembrane
HMG-CoA leads to the formation of an intermediate known as ____ acid from its precursor, HMG-CoA.
Mevalonic
____ are competitive inhibitors of HMG-CoA reductase
Statins.
Cellular response of statins is to generate more ____ receptors to scavage ____/cholesterol from the bloodstream.
LDL;LDL
What is a common statin, competitive inhibitor of HMG-CoA reductase?
Atorvastatin
Statins are ____ extraction drugs that are rapidly absorbed and processed by first pass metabolism.
high
Does cholesterol synthesis take place during sleep or when you are awake?
during sleep
____ are agonists of PPArs, peroxisome proliferator-activated receptor (intracellular receptors)
Fibrates
Fibrates is used to treat what?
dyslipidemias
PPARs bind to their ligand –> receptors ____ with RXR (retinoic acid receptors) —> increase expression of ____ lipase.
dimerize; lipoprotein
Increased expression of lipoprotein lipase leads to ____ breakdown of triglycerides in ____ receptors and uptake of fatty acids as fuel in peripheral tissues.
increased; VLDL
