RESUMEN
Lp(a) is a novel cardiovascular risk factor resembling an LDL particle. It includes a copy of apolipoprotein (a) [apo(a)], whose molecular weight is dependent on the number of genetically encoded kringle IV type 2 (KIV-2) repeats and inversely related with Lp(a) plasma concentration and risk. The reason for this inverse relationship is unclear and, particularly, there are no data regarding the size of Lp(a) particles carrying apo(a) with different molecular weights. The aim of the present work was to explore if a relationship existed between apo(a) molecular weight and particles size in Lp(a) samples carrying 20, 25 and 28 KIV-2 repeats (K20, K25 and K28, respectively). Dynamic Light Scattering (DLS) measurements were performed on affinity-purified Lp(a). A preliminary finding was that particles were typically distributed into three different size groups instead of the single one expected. No difference in average particle size between Lp(a) carrying different apo(a) isoforms was found. However, the percentage of medium-sized particles in each sample was found to be inversely related to the number of KIV-2 repeats (R2=0.99), with a clear predominance in K20 (58.53%). These data deserve further investigations, as they might be potentially relevant to explain the pathogenic role of low molecular weight Lp(a) isoforms.
RESUMEN
Lipoprotein (a) [Lp(a)] is a novel independent cardiovascular risk factor and it includes, beyond apoB100, apolipoprotein (a), whose molecular weight is dependent on the number of genetically encoded kringle IV type 2 repeats and inversely related with Lp(a) plasma concentration. Risk thresholds for molecular weights have been proposed, but there is not a full consensus and the role of the different isoforms in pathogenesis has not yet been clarified. The aim of the present work is to explore the biological effect of low and high molecular weight Lp(a) isoforms on cultured cells. Real-time impedance analysis has been performed on model cell lines of atherogenesis and Lp(a) metabolism (THP-1, HUVEC, HASMC and HepG2) using affinity purified Lp(a) with 22 (low number) and 31 (high number) kringle IV type 2 repeats, respectively. Normalized Cell Index data show that all the cell lines tested are modified by Lp(a), though with a variable intensity. Low and high molecular weight Lp(a) isoforms at similar concentrations can exert opposite modifications on the impedance kinetics of different cell lines. These data suggest that purified Lp(a) can modify the behaviour of adherent cell lines, an effect which can be detected as impedance variation and which is influenced by its specific isoform.