So far we have been talking only about the lipoprotein particle structure, or what we call the proteome. If we draw together all of the information from the literature concerning the different proteins present in the proteome of HDL, we find 20 or so that are consistently identified by proteomic analysis. Clearly apoA-I and apoA-II are always included, but we also find proteins like apoE, apoM, apoD; we also find the C proteins, which are very important to certain lipolytic reactions, of course – apoC2 is a catalyst of an activator of lipoprotein lipase, apoC3 is an inhibitor of lipoprotein lipase, etc. The 3 proteins on the bottom in the Figure – PAF acetylhydrolase (PAF-AH, also known as Lp-PLA2) and the paraoxonases – are able to degrade oxidized phospholipids and to attenuate their pro-inflammatory activity, which is clearly of major relevance to the pathophysiology of atherosclerosis.
In other words, this abbreviated list of proteins consistently found in the HDL proteome reveals the biologic relevance of these different proteins and underscores the fact that they all possess distinct biological activities.
Finally, there is a very special protein in the HDL3 particle, apoL1, that pertains to a highly specialized function of HDL3, the inactivation of trypanosomes. Trypanosomes underlie the sleeping sickness disease, which is so frequently found in Sub-Saharan Africa. ApoL1 is a very specialized protein that is able to penetrate the trypanosome parasite to inactivate its lysosomes by drilling a pore in the membrane, causing them to lyse as a consequence of this very specialized biological activity of apoL1.
The result of all this research is that it is becoming clear that there are specific clusters of proteins within HDL subpopulations that exert very specific functions, and many of those functions are relevant to the pathophysiology of atherosclerosis. Of course, atherosclerosis was not much of a problem, earlier in evolution, and so it is of much interest that some of the specific functions of HDL that are a product of these special subpopulations of proteins are also protective against infection – a function that many of us believe was, in fact, originally one of the major roles of HDL in evolution.
J Clin Lipidol. 2011; 5(6).