Read on Twitter
1/🧵 If Plaque #ApoB-48 > #ApoB-100
Quite a rabbit hole so far...
First, let me say that data on this has been a bit limited. But *IF* we do ultimately confirm there are more ApoB-48 (B48) than ApoB-100 (B100) in ASCVD plaque, it would be a very big deal.
Let's unpack...
Quite a rabbit hole so far...
First, let me say that data on this has been a bit limited. But *IF* we do ultimately confirm there are more ApoB-48 (B48) than ApoB-100 (B100) in ASCVD plaque, it would be a very big deal.
Let's unpack...
2/ First, thanks to @TuckerGoodrich for pinging me on these pubs and pressing the discussion.
But also credit to @CaloriesProper on tweeting this a couple years ago (I missed it then)
To understand why this would be so important if true, some review...
But also credit to @CaloriesProper on tweeting this a couple years ago (I missed it then)
https://twitter.com/CaloriesProper/status/1408917991425822726
To understand why this would be so important if true, some review...
3/ B48 and B100s are the major proteins on chylomicrons (CMs) and VLDLs, respectively.
CMs mostly carry lipids from the small intestine to the bloodstream (lipids consumed), VLDL mostly carry lipids from storage; predominantly from adipose stores.
See full linages here 👇
CMs mostly carry lipids from the small intestine to the bloodstream (lipids consumed), VLDL mostly carry lipids from storage; predominantly from adipose stores.
See full linages here 👇
4/ However -- there's been some recent shaking up of this assumption.
For example, there appears to be some "repurposed" of B48 by the liver to send out as VLDL instead of B100 (per study from above)
There's also some other notables I won't cover here.
For example, there appears to be some "repurposed" of B48 by the liver to send out as VLDL instead of B100 (per study from above)
There's also some other notables I won't cover here.
5/ Regardless, all sources agree B100 lipoproteins comprise well over 90% of the total betalipoproteins in circulation.
Thus, conversely, B48 lipoproteins comprise well under 10%.
Thus, conversely, B48 lipoproteins comprise well under 10%.
6/ So given this, why wouldn't plaques reflect a similar composition to that of the bloodstream?
Given the prevailing Response to Retention hypothesis, we'd expect random infiltration of betalipoproteins, which would certainly favor the B100 linage.
Given the prevailing Response to Retention hypothesis, we'd expect random infiltration of betalipoproteins, which would certainly favor the B100 linage.
7/ It actually gets odder still when considering scale.
The long held assumption is that LDL is particularly atherogenic due to its smaller size for infiltration compared to larger particles. But CM and CM remnants are of the largest particles, each with B48 (where LDL is B100)
The long held assumption is that LDL is particularly atherogenic due to its smaller size for infiltration compared to larger particles. But CM and CM remnants are of the largest particles, each with B48 (where LDL is B100)
8/ Lastly, I have to draw focus to the fact that where these particles are intact, they are TG-poor.
It's speculated this might have occurred postmortem.
... But what if it wasn't?
It's speculated this might have occurred postmortem.
... But what if it wasn't?
9/ I continue to speculate the endocytose-ing of betalipoproteins by endothelial cells could be relevant for the immune response with respect to macrophages. I have a few different hypotheses on this, but active TG usage is one, which is why I'm very interested in its depletion.
10/ Regardless, I certainly think this is an area worth confirming with further research. It definitely opens up a lot more questions than answers if it proved true B48 outnumbered B100 in these plaques.
• • •
Missing some Tweet in this thread? You can try to
force a refresh
