Here is a graph showing ~4-fold increased risk at >95th-percentile Lp(a) level.
Lp(a) is a lipoprotein.
A lipoprotein has three parts: a core containing triglycerides and cholesterol, a shell containing phospholipids, and a skeleton holding the shell together called apolipoproteins.
Attached is an image of a generic lipoprotein. 11/n
So we need to know what LDL is, to know what Lp(a) is.
LDL is a lipoprotein, the same as the above. However, the apolipoprotein that holds LDL together is called apoB. The apoB is what makes LDL LDL. 12/n
Lp(a) = LDL + apo(a).
Thas it mayne. wolfsonintegrativecardiology.com/lpa-geneticall… 16/n
Inch-long spikes. Added to the baseball stitching. That help the particle shear through blood vessel walls.
So just eat healthy, right?
Alas, if only it were so. 17/n
How does any of this make sense?
Why would evolution do this?
Turns out, apo(a) came from gene duplication of plasminogen, which is responsible for blood clotting.
What's gene duplication? As it sounds. During evolution plasminogen was copied twice in DNA by mistake.
As you can see:
After Hugh Jackman says, "what the hell are you?" if you listen very closely, you will hear the response, "Lipoprotein (a)..."
And European hedgehogs, which evolved Lp(a) independently. ncbi.nlm.nih.gov/pubmed/28888913 29/n
If you find any of this confusing, go back to the previous tweets. And send a reply or DM if you have questions.
But with this background, we can start to sketch out why different humans have different levels of genetically determined Lp(a). And what Lp(a) does. 37/n
But first, a brief review with some a couple of new figures. As you can see below, the number of KIV2 copies dramatically affects the size of apo(a).
Figure (b) is the meat. As apo(a) gets bigger, Lp(a) blood levels go down. And vice versa. 40/n ncbi.nlm.nih.gov/pubmed/22998429
ApoB also happens to be apo(a)'s binding partner.
Now, the review of CVD. 73/n
But the lipoproteins aren't simply cargo trucks. No. Because there is the constant threat of invasion by bandits. 78/n
The threat of bandits is constant. So even the cargo trucks are armed. Like this, the tanker from Mad Max 2. With all the same moral ambiguity as in the film. 81/n
The charged end interacts with water, which is polar.
Charged parts of molecules interact with polar molecules.
The nonpolar end, the fatty acid end, interacts with the fatty cargo inside.
As we see, they are 50% triglycerides. If we look only at the core, they are 75% trigs, 25% cholesterol. They are produced in the liver and pass their cargo in a manner similar to chylomicrons learn.ppdictionary.com/exercise_and_l… 100/n
Now for Lp(a), a protein similar to LDL but synthesized through its own, unique pathway. 104/n
LDL is defined by apoB by itself.
So is Lp(a) simply a modification of LDL as this image by Wolfson implies?
No. wolfsonintegrativecardiology.com/lpa-geneticall… 107/n
Lp(a) is formed via an entirely different synthetic pathway from LDL. ncbi.nlm.nih.gov/pmc/articles/P… 108/n
Lp(a) is not LDL with apo(a) attached. It follows its own rules.
And in more ways than this. 109/n
Here is an image of Lp(a) that could be hedgehog or human. 110/n
apoB is the apolipoprotein that is the best surrogate for LDL particle number. 111/n
And surprise: apoB may be a better predictor of CVD risk than LDL cholesterol concentration. circoutcomes.ahajournals.org/content/4/3/337 112/n
Here is a panel from 2016. ApoA1, apoB, and apoE in progressively more damaged brain aneurysms. ncbi.nlm.nih.gov/pubmed/27283327 126/n
apoE overlaps with apoA1, a marker of HDL, but not with macrophages. This suggests that the apoE is coming from HDL aggregation in the vessel walls. Ouch.
So for the quantification, they took images from... circ.ahajournals.org/content/98/6/5… 135/n
And 80 images from the 20 segments from the additional 8 patients.
What did they find? (A-first set of pts; B- second set.) circ.ahajournals.org/content/98/6/5… 136/n
Nonetheless, let's follow these findings. Perhaps they will turn around.
Next, investigators wanted to test whether it was... 139/n
Christ. circ.ahajournals.org/content/98/6/5… 143/n
Is apoE in the atherosclerotic plaque a mere epiphenomenon, i.e. not a cause but a consequence of CVD? ncbi.nlm.nih.gov/pubmed/27755538 146/n
These are questions to keep in mind moving forward. 147/n