Quantitation of lipoprotein (a) after lysine-sepharose chromatography and density gradient centrifugation.

Publisher Summary Lipoprotein (a) [Lp(a)] is a novel low-density lipoprotein (LDL)-like lipoprotein whose plasma concentration can vary over 100-fold among different individuals. These concentration differences are inherited and controlled to greater than 90% by the apolipoprotein (a) [apo(a)] gene. Lipoprotein (a) is polymorphic in nature because apo(a) isoforms vary in the number of kringle 4 domains and the abundance of kringle 4 repeats in the apo(a) gene is inversely correlated to the concentration of Lp(a). Compared to other lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein (HDL), plasma levels of Lp(a) are relatively small that creates a problem in the purification of Lp(a) from the more abundant lipoproteins. The presence of the disulfide-linked, heavily glycosylated apolipoprotein (a) shifts the density distribution of the LDL like Lp(a) particles intermediate between that of LDL and HDL. The size of apolipoprotein(a), together with Lp(a) lipid, are major determinants of Lp(a) density. Individuals that express two apo(a) isoforms will have a density profile, in which Lp(a) particles may be well separated, when the difference in size between the two apo(a) isoforms is large, but may not have well-separated bands on the density gradient when size differences are small. Separation is also affected by the relative concentration of the two Lp(a) species. Because the density distribution of Lp(a) overlaps those of LDL and HDL, one cannot isolate Lp(a) encompassing its complete density spectrum, without including isopycnic LDL and HDL particles. Similarly, when separation methods are used that utilize size, such as gel filtration, in the purification of Lp(a) from LDL and HDL, Lp(a) cannot be completely separated from LDL because of the overlapping size distributions.