Genes and Atherosclerosis Flashcards
Is atherosclerosis a multifactorial disease?
YES
What is the estimated risk effect of each single genotype?
1.12 - 1.75 (where 1.0= no change at all, but they can add if multiple genes are involved).
Is someone with familial combined hyperlipidemia monogenetic?
NO. There is more than one gene involved.
For what percentage to genes account in CAD?
10-20%
What are chylomicrons?
lipoprotein particles that are made in the endoplasmic reticulum of enterocytes/epithelial cells of the small intestine. They are derived from dietary lipids and contain up to 90% of triglycerides (TG»Chol). Their function is to transport lipids absorbed from the intestine to adipose, cardiac, and skeletal muscle tissue, where their TG components are hydrolyzed by the activity of lipoprotein lipase to FAs and glycerol to be absorbed by the tissue.
What lone protein does a nascent chylomicron contain?
ApoB-48.
What is important to remember about the ApoB proteins?
ApoB-48 and ApoB-100 come from the same gene, but a stop codon separates the two.
What is lipoprotein lipase (LPL)?
extracellular enzyme that lines lumen of blood vessels and hydrolyzes TG down to FAs and glycerol. The glycerol gets used as energy and the FAs go into the epithelial cell to be packaged.
What does HDL donate to chylomicrons?
ApoCII and ApoE
What happens when a large portion of the chylomicron TG core has been hydrolyzed?
Chylomicron remnants (TG:Chol= 1:1) remain and are taken up by the liver and dock via ApoE, thereby transferring dietary fat also to the liver.
Is triglyceride (TG) a risk factor?
YES. Normal fasting levels= 75 mg/dL
What genes are directly involved with TG levels?
ApoA-5, ApoCI, II, III, and lipoprotein lipase (LPL)
Is ApoA-5 good or bad, and why?
GOOD because it lowers TG levels :)
Is ApoC-I good or bad, and why?
GOOD because it may activate PCAT, which helps HDL to do its job :)
Is ApoC-II good or bad, and why?
GOOD (only at intermediate levels) because it activates LPL :)
Is ApoC-III good or bad, and why?
BAD because it inhibits TG hydrolysis by LPL and inhibits VLDL clearance :(
It may contribute to atherosclerotic plaques.
Is lipoprotein lipase good or bad?
GOOD because it releases apoprotein and phospholipids for HDL to reuse.
*S447X variant enhances LPL :)
Where is VLDL made?
by the liver cells
What makes up VLDL?
mainly FAs in the form of TGs from nascent chylomicrons
What Apoproteins does VLDL contain?
Apo-B100, (ApoCII, and ApoE it will aquire from HDL)