PURPOSE Mutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I(L202P) and apoA-I(K131del) , are present on plasma HDL particles derived from heterozygote carri...

OBJECTIVE To compare the abilities of human wild-type apoA-I (WT apoA-I) and human apoA-I(Milano) (apoA-I(M)) to promote macrophage reverse cholesterol transport (RCT) in apoA-I-null mice infected with adeno-associated virus (AAV) expressing either WT apoA-I or apoA-I(M). METHODS AND RESULTS WT apoA-I- or apoA-I(M)-expressing mice were intraperitoneally injected with [H(3)]cholesterol-labeled...

Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA...

The distribution of apolipoproteins (apo) A-I, A-IV, and E in sera of fed and fasted rats was studied using various methods for the isolation of lipoproteins. Serum concentrations of apoA-I and apoA-IV decreased significantly during fasting (16 and 31%, respectively), while apoE concentrations remained essentially the same. Chromatography of sera on 6% agarose columns showed that apoA-IV is pre...

Apolipoproteins A-I and A-II comprise approximately 70 and 20%, respectively, of the total protein content of HDL. Evidence suggests that apoA-I plays a central role in determining the structure and plasma concentration of HDL, while the role of apoA-II is uncertain. To help define the function of apoA-II and determine what effect increasing its plasma concentration has on HDL, transgenic mice ...

Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins apo-A-I and apoA-II in patients with Tangier disease are approximately 1% and 7% of those in normal subjects, respectively. Previous stud...

The genes coding for three of the proteins of the lipid transport system, apolipoproteins A-I (apoA-I), C-III (apoC-III), and A-IV (apoA-IV), are closely linked and tandemly organized as a multigene family in the human genome. The evolution of this multigene family was studied by cloning and extensive restriction mapping analysis of an approximately 20-kilobase genomic DNA fragment containing t...

The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models. Adenovirus-mediated gene transfer of apoA-IV in apoA-I(-/-) mice did not change plasma lipid levels. ApoA-IV floated in the HDL2/HDL3 region, promoted the formation of spherical HDL particles as determined by electron microscopy, ...

In human serum, polymorphism of apoA-II predominantly in HDL3 could be demonstrated. HDL3-apoA-II was composed of four isoproteins, each with a molecular weight of 8600 (reduced form) and identical immunological properties. The isoproteins are designated apoA-II-1 (pI 5.16), apoA-II-2 (pI 4.89) corresponding to the already known apoA-II monomer band, apoA-II-3 (pI 4.58), and apoA-II-4 (pI 4.31)...

Studies with mice have revealed that increased expression of apolipoprotein A-II (apoA-II) results in elevations in high density lipoprotein (HDL), the formation of larger HDL, and the development of early atherosclerosis. We now show that the increased size of HDL results in part from an inhibition of the ability of hepatic lipase (HL) to hydrolyze phospholipids and triglycerides in the HDL an...