MDCO-216 is a complex of dimeric ApoA-IMilano and @entity37584 ( @entity33170 ), previously shown to reduce @entity731 plaque burden. Here we studied the effect of incubation of @entity1 plasma or serum with MDCO-216 on @entity165 efflux capacity from @entity19 cells, on prebeta-1 high density lipoprotein (prebeta-1 HDL) and on HDL size assessed by proton nuclear magnetic resonance ((1)H-NMR). MDCO-216 incubated in buffer containing 4% human serum albumin stimulated both @entity21123 -mediated efflux and @entity21123 -independent @entity165 efflux from J774 macrophages. When incubated with human serum a dose- and time-dependent synergistic increase of the @entity21123 -mediated efflux capacity were observed. Using a commercially available ELISA for prebeta-1 HDL, MDCO-216 as such was poorly detected (12-15% of nominal amount of protein). Prebeta-1 HDL was rapidly lost when @entity1 plasma alone is incubated at 37  C. In contrast, incubation of @entity1 plasma with MDCO-216 at 37  C produced a large amount of new prebeta-1 HDL. Native 2D electrophoresis followed by immunoblotting with an @entity1675 antibody, which also detects @entity1675 Milano, confirmed the increase in prebeta-1 HDL upon incubation at 37  C. With the increase of prebeta-1 HDL, the concomitant disappearance of the small alpha-3 and @entity1293 HDL and MDCO-216 and an increase in the large @entity6927 and alpha-2 HDL were observed. Immunoblotting with Mab 17F3 specific for @entity1675 Milano showed the appearance of @entity1675 Milano in @entity6927 and alpha-2, but not in prebeta-1 HDL. (1)H-NMR analysis of plasma incubated with MDCO-216 confirmed rapid disappearance of small-sized HDL particles and increase of medium- and large-sized HDL particles accompanied with a decrease in total HDL particle number. In conclusion, incubation of @entity1 plasma or serum with MDCO-216 strongly enhanced @entity21123 -mediated @entity165 efflux, caused a strong increase of prebeta-1 HDL, and drastically changed the distribution of HDL subpopulations. Overall, the results are in line with the hypothesis that MDCO-216 fuses with small alpha-migrating HDL particles forming larger particles containing both @entity1675 WT and @entity1675 Milano, meanwhile liberating the endogenous wild-type @entity1675 which enriches prebeta-1 HDL subpopulation.

Incubation of MDCO-216 (ApoA-IMilano/ XXXX ) with Human Serum Potentiates @entity21123 -Mediated @entity165 Efflux Capacity, Generates New Prebeta-1 HDL, and Causes an Increase in HDL Size.

@entity1 :: ('9606', 'Species') :: ['human'] @entity37584 :: ('MESH:C028694', 'Chemical') :: ['palmitoyl oleoyl phosphatidylcholine'] @entity6927 :: ('146', 'Gene') :: ['alpha-1'] @entity19 :: ('10090', 'Species') :: ['J774'] @entity33170 :: ('MESH:C065191', 'Chemical') :: ['POPC'] @entity21123 :: ('19', 'Gene') :: ['ABCA1'] @entity1675 :: ('335', 'Gene') :: ['ApoA-I', 'apoA-I'] @entity1293 :: ('3476', 'Gene') :: ['alpha-4'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity33170 :: (MESH:C065191,Chemical) :: ['POPC']
