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Apolipoprotein A-V (apoA-V) is a recently discovered apolipoprotein that appears to have a role in plasma triglyceride (TG) transport. We have developed an ELISA for apoA-V using monoclonal antibodies that has a lower limit of detection of 0.3 ng/ml and linearity up to 20 ng/ml. The ELISA was then used to quantify plasma apoA-V in 196 healthy subjects and 106 patients with insulin-resistant diabetes mellitus. In the healthy subjects, total apoA-V concentration was 179.2 ؎ 74.8 ng/ml, and it was greater in females than in males ( P Ͻ 0.005). It was correlated positively with the plasma HDL cholesterol ( r ‫؍‬ 0.32, P Ͻ 0.0001), apoA-I ( r ‫؍‬ 0.27, P ‫؍‬ 0.0001), and apoE ( r ‫؍‬ 0.18, P ‫؍‬ 0.011) concentrations and negatively with plasma TG concentration ( r ‫؍‬ ؊ 0.22, P ‫؍‬ 0.021). In relation to single nucleotide polymorphism 3 ( ؊ 1131C/T) of the apoA-V gene, apoA-V concentration was higher in the T/T type than in the C/C type ( P Ͻ 0.01). Plasma TG concentration was lower in the T/T type than in the C/C or C/T type ( P Ͻ 0.05). ApoA-V concentration was lower in the diabetic patients (69.4 ؎ 44.3 ng/ml; P Ͻ 0.01) than in the healthy controls. Plasma triglyceride (TG) levels are influenced by both genetic and environmental factors and are a major independent risk factor for coronary heart disease (1, 2). Plasma TG concentration is influenced by many factors. These include apolipoproteins A-I, A-IV, C-II, and C-III, LPL, LCAT, cholesteryl ester transfer protein, and phospholipid transfer protein (3-11). These factors and their associated gene-environment interactions are of importance in the pathogenesis of coronary heart disease.Apolipoprotein A-V (apoA-V) has recently been identified by comparative sequencing of human and mouse DNA and is located ‫ف‬ 27 kb distal to the apoA-IV gene in the APOA1/C3/A4 gene cluster on chromosome 11q23 (12). ApoA-V, shown to be expressed mostly in liver and independently named regeneration-associated protein 3, is upregulated after the early phase of liver regeneration after hepatectomy in rat (13). In mice overexpressing the human apoA-V gene, TG concentrations decreased by 50-70%, and in apoA-V gene knockout mice, plasma TG concentrations increased ‫ف‬ 4-fold (12-14). These results suggest that apoA-V expression may strongly influence, and be negatively associated with, plasma TG concentrations. ApoA-V both enhances lipoprotein lipase-mediated hydrolysis of plasma TG and inhibits hepatic VLDL-TG production (15). ApoA-V also stimulates the efflux of cholesterol from cells by a mechanism independent on the ABCA1 protein, as do other exchangeable apolipoproteins, such as apoA-I and apoA-IV (16). It was recently described that apoA-V mRNA is regulated by peroxisome proliferator-activated receptor ␣ agonists (17,18) and that the liver X receptor ligand T0901317 decreases apoA-V mRNA through the activation of sterol-regulatory element binding protein 1c (SREBP-1c) (19). These results raise the possibility that some TG-lowering agents, such as fenofibrate, may act by alte...

An efficient route for delivering specific proteins and peptides into neurons could greatly accelerate the development of therapies for various diseases, especially those involving intracellular defects such as Parkinson disease. Here we report the novel use of polybutylcyanoacrylate nanoparticles for delivery of intact, functional proteins into neurons and neuronal cell lines. Uptake of these particles is primarily dependent on endocytosis via the low density lipoprotein receptor. The nanoparticles are rapidly turned over and display minimal toxicity to cultured neurons. Delivery of three different functional cargo proteins is demonstrated. When primary neuronal cultures are treated with recombinant Escherichia coli ␤-galactosidase as nanoparticle cargo, persistent enzyme activity is measured beyond the period of nanoparticle degradation. Delivery of the small GTPase rhoG induces neurite outgrowth and differentiation in PC12 cells. Finally, a monoclonal antibody directed against synuclein is capable of interacting with endogenous ␣-synuclein in cultured neurons following delivery via nanoparticles. Polybutylcyanoacrylate nanoparticles are thus useful for intracellular protein delivery in vitro and have potential as carriers of therapeutic proteins for treatment of neuronal disorders in vivo.