Lipoprotein(a), a prickly subject

Convergent evolution is a fascinating subject. Lipoprotein(a) has been independently evolved at least twice, not only to produce a remarkably similar (but not identical) molecule each time, but on both occasions it has been by a modification of the same gene, that for plasminogen. The two groups with well characterised Lp(a) are of course old world primates (including man) and the hedgehog. You thought the non primate was the guinea pig? Well, I've not been able to find any replication of Pauling and Rath's work with lipoprotein(a) in guinea pigs and the people who did the work with hedgehogs have looked for the apoprotein(a) gene in guinea pigs, pretty thoroughly... and without success.

What is lipoprotein(a)? It's perhaps best described as a super LDL. Just imagine taking a lethal LDL particle and wrapping it up in a second protein, apo(a), which is not only specifically designed to bind the whole lipid particle to the fibrin present in a blood clot, but which also inhibits clot dissolution. On top of that (could it get worse?) apo(a) is heavily and specifically glycosylated with a sticky sugar coating which will bind to the arterial wall. Hmmmm, if you wanted to clog an artery with lipid, this has got to be your glue!

A quick trip to St Tiggywinkles Hedgehog Hospital would be expected to reveal cages of recuperating hedgehogs, victims of strokes, aortic aneurisms, heart attacks, peripheral vascular disease, all of the problems associated with elevated Lp(a) in humans. In truth my guess is that most of them (the hedgepigs) will actually be victims of road traffic accidents, lung worm infection (a killer in hedgehogs) and late summer birthed toddlers who won't overwinter successfully in the wild.

Perhaps Lp(a) in hedgehogs is different to Lp(a) in humans. It has certain structural differences, but it still acts in as an inhibitor of clot dissolution in models based on human tissue. The fact that it doesn't seem to cause vascular problems in hedgehogs is all the more surprising when you realise that it is THE bulk lipid transport particle in hedgehogs!

The other very strange thing about Lp(a) is that it tends to be rather good for you if you (as a human) make old bones:

"lipoprotein(a) elevation in centenarians, in the absence of other coronary artery disease risk factors, appears as a positive survival factor"

It's worth noting that many of the risk factors for heart disease are turned on their head anyway in the elderly, once you look at all cause mortality. If you are over 65 years old, white or African-American then better think twice about popping that statin! You might end up in that lowest quartile of LDL cholesterol, maybe down at 60mg/dl:

"hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile"

Just to simplify, low LDL cholesterol=death. That got missed out of the conclusion line! For hispanics, all lipids were irrelevant once you cracked 65 years of age, ie high LDL is not protective in elderly hispanics, nor is it a problem. Of course this is only New York, things may be different in other places. Maybe.

Well, that got me side tracked. Back track with Lp(a) next post.

Peter