Biochem lipids question

[linkin06]

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why is it that Type 1 dyslipidemia (hyper-chylomicronemia) doesn't result in increased risk for atherosclerosis? ^ TG and cholesterol seems bad to me...

 

[Phloston]

That's a good question. I'm not 100% sure.

I would guess that it's 1) a combination of the fact that moieties with greater cholesterol % demonstrate increased likelihood of transcytosis of the tunica intima (i.e. chylomicrons are less likely to embed within the tunica intima relative to VLDLs), and 2) LDL-receptors are still functional/present, so even if cholesterol is elevated, it probably is not to the same extent as with dyslipidaemia type-IIa.

The latter is probably likely. However the only reason I guess the former is because it's classically VLDLs, not chylomicrons, that normally transcytose the tunica intima anyway.

Once again, that's just an assumption. I'm just as interested as you are to know that answer.

 

[linkin06]

so you feel cholesterol > triglycerides in causing probs?

haven't reviewed cardio yet, but i just remembered we shoot for <100 triglycerides for atherosclerosis.

 

[Phloston]

I'm not jumping to any conclusions regarding triglycerides vs cholesterol. The #1 reason is likely just bc the LDL-receptor is merely present and functional. That probably doesn't mean the risk for atherosclerosis isn't augmented in hyperchylomicronaemia, but it's likely just not nearly to the same extent as it is with type-IIb.

 

[loveoforganic]

I was under the impression that in type i you had no means by which to free all the lipids from the chylomicrons, so you have hyperchylomicronemia (and associated acute pancreatitis, xanthomas eruptions, etc.), but not anything involving the handling of individual lipid molecules as would be required for atherosclerosis development. In type ii, you have increased LDL in circulation and you do have the means of delivery to peripheral tissue

 

[AndyRSC]

The hypotheses presented so far are plausible. I'll chip in one more:

Atherosclerosis stems to a great extent from oxidation of the LDL apolipoprotein B100 by ROS in the bloodstream. Because there is only one APOB100 per LDL particle, any modification to the APOB100 makes the LDL unable to bind LDL receptors and appears foreign to the immune system. These molecules are scavenged by macrophages (using scavenger receptor-A), and since SR-A is not down-regulated by cholesterol, these cells are able to accumulate large amounts of cholesterol (foam cells) before spilling it as they die.

Clearly, elevated LDL will result in competition at the LDL receptors of peripheral tissues and prolong the circulating time of LDL in the bloodstream, increasing the opportunity for APOB100 to become oxidized or otherwise modified, and increasing the opportunity for them to be scavenged by SR-A. Obviously, type IIA familial dyslipidemia inflates these statistics. Type I dyslipidemia, not subject to same limitations, does not. Furthermore, LDL contains 100-fold more cholesterol per particle than chylomicrons.

Edit: a quick review of literature does show, however, a positive relationship between chylomicron elevation and atherosclerosis, although "there have been as yet no clinical studies that have investigated the relationship between apo B48 and cardiovascular events."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189596/

 

[linkin06]

discussed it w/ a buddy. he was saying that atherosclerosis specifically is initiated by LDL getting into the intima => inflammation

so LDL might be the issue here, not so much the cholesterol and/or triglycerides. a simpler explanation that might not even be right, but it'll help me remember it.

 

[Morsetlis]

so you feel cholesterol > triglycerides in causing probs?

haven't reviewed cardio yet, but i just remembered we shoot for <100 triglycerides for atherosclerosis.

Hypertriglyceridemia is typically less of a concern compared to hypercholesterolemia. I actually had HyperTAG and reduced it to below average through a combination of Grenadian food and med school.

Specifically, cholesterol is susceptible to oxidation: It has free -OH endings. A TAG does not.

 

[Phloston]

cholesterol... has free -OH endings. A TAG does not.

Good point there.

 

[Alvarez13]

discussed it w/ a buddy. he was saying that atherosclerosis specifically is initiated by LDL getting into the intima => inflammation

so LDL might be the issue here, not so much the cholesterol and/or triglycerides. a simpler explanation that might not even be right, but it'll help me remember it.

The fatty streak!

Lol, that sounds like something you do after eating a bunch of burgers and getting blasted on PBR.