"Lp(a) levels are low at birth and rise significantly between 0 and 7 days post partum; in this newborn population, a continuous rise of the mean Lp(a) levels was observed until 180 days"
Well, that's it. The smoking gun of arteriosclerosis. As we know, arteriosclerosis is essentially non existent for humans in-utero and it starts soon after birth (in the 1950s anyway, we may do better at damaging unborn children nowadays). Lp(a) starts low at birth and rises soon after. You only need to be a cardiologist to see the obvious cause and effect here.
OMG it must be so embarrassing to realise that LDL-C has nothing to do with the process, it's been that nasty Lp(a) all the time!
So the obvious explanation must be that Lp(a) worms its way through the arterial endothelium and rips and tears the elastin fibres of the intima to shreds. Simple and utterly plausible. Probably carries a flick-knife.
Except for the tissue transglutaminase (TTG) issue.
We have all heard of this enzyme as an antibody-ligand when testing for coeliac disease, but what does TTG actually do?
Well there is an awful lot of information in this paper. This is what they looked at:
"Because of its intimate interaction with fibrin and/or cell surface oriented structures, we asked whether Lp(a) could be a substrate for transglutaminases (e.g. Factor XIII, tissue transglutaminase). These enzymes catalyze cross-linking between endo-gamma-glutaminyl and endo-epsilon-lysyl residues of proteins (16) resulting in irreversible homo or heteropolymerization of susceptible proteins."
Note the heteropolymerization. Hetero means mixed. If TTG really acts on Lp(a), it doesn't just bind it to more Lp(a), it will bind it to other TTG substrate proteins too. Many of the other TTG substrates are physically part of the cement between cells. Molecules like fibronectin.
"First, substrate specificity was compared with known transglutaminase substrates including fibronectin (17) and alpha 2-plasmin inhibitor (30) and substrates of poor or unknown transglutaminase susceptibility including IgG, alpha 1-proteinase inhibitor, and albumin. This showed that Lp(a) had amine acceptor qualities comparable to that of fibronectin and alpha 2-plasmin inhibitor where as IgG, alpha 1-proteinase inhibitor and albumin failed to incorporate significant amounts of DSC."
So Lp(a) will heteropolymerise with fibronectin:
"FXIII or tissue transglutaminase may catalyze cross-linking and deposition of Lp(a) to surface oriented structures (e.g. connective tissue matrix proteins) and/or cell surfaces."
If you are wondering what fibronectin really does, from wiki:
"fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans" (as well as intergins). Oh, look, proteoglycans...
And integrins, from wiki:
"Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and thereby define cellular shape, mobility, and regulate the cell cycle."
So TTG binds Lp(a), almost certainly to fibronectin, one the main proteins which glue our tissues together. Lp(a) is not randomly sticky. It is enzymatically and specifically integrated in to the matrix of exposed extracellular material in the wall of a damaged artery.
If we reject the hypothesis that Lp(a) circulates with an elastin-targeted flick-knife in its pocket, we can look at the specific and deliberate incorporation of Lp(a) in to a cross-linked network of tissue proteins. This looks like an emergency repair kit to me. Elastin is broken by mechanical stress. Birth, growth, pulsation of arteries, hypertension, relative movement of the supply artery against fixed arteries like the intercostals, branch points in arteries etc are all mechanical stressors. Broken elastin implies stretching of the artery beyond what the elastin will tolerate. Damage to the elastin comes with damage to the endothelium. Disrupted endothelium exposes extracellular matrix and needs a clot to patch it and the clot needs strengthening. An area of damage intrinsically means that the location was too weak. Adding some fibrous tissue and a stronger muscle around damage is an adaptive stratagem in an injury-disrupted provenly-weak arterial area.
Looking at Lp(a) as a repair kit you can make certain predictions, especially if the repair kit is rather helpful.
First is that not having any Lp(a) is bad. Well, we know that's the case.
Next is that having some Lp(a) is good, we know that too from the same graph.
If you are genetically well endowed (with repair kits) they will not show up as repair patches on your arterial wall unless you are actively damaging that arterial wall. ie High Lp(a), (genetic low kringle IV repeat numbers) means nothing if you are not damaging your arteries. Thanks to Kurt for that anecdote!
If you do lots of damage, you will need lots of repair kits. Lp(a) goes up with carb intake and down with saturated fat intake. Check DELTA.
EDIT: Also from DELTA, your body anticipates damage, or detects actual damage, if you replace the saturated fat of the SAD with monounsaturated fat. So it makes more Lp(a). That's it. You liver is worried by MUFA. Extra virgin olive oil is heart healthy? Dump it for lard or, better still, beef dripping! Less plant antioxidants for your liver to eliminate too.
If you do some thing stupid, like pushing your carb intake beyond what is acceptable (even as a non industrialised form of carbs), your liver will make extra repair kits and they will be both needed and used on your arteries. Remember the vegetarian Bantu farmers getting nearly 90% of their calories from complex carbohydrate? Blood pressure rises with age. Not so at 70% from carbs in the Bantu fishermen.
The more damage, the more repair kits get made, the more repair kits get used. The more damage, the more blood pressure rises with age.
Lp(a) rises soon after birth because birth is when pressure induced damage starts. Life, especially being born, is a damaging process. Some lives are more damaging than others.
Are you going to blame the rising blood pressure on the repair kits? Have you forgotten to take your statin today? You may also have forgotten where you left your blood pressure tablets.
BTW, obviously these stable fibrous arteriosclerotic lesions have nothing to do with heart attacks. Heart attacks happen in the elderly, not in infants!