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Received on July 27, 2004
Accepted on October 15, 2004
Lipids, Lipoproteins, and Cardiovascular Risk Factors |
1 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN
2 Linco Diagnostic Services, St. Charles, MO
* To whom correspondence should be addressed. E-mail: konrad_robert{at}lilly.com.
Background: The recently discovered apolipoprotein A5 (ApoA5) is fast gaining attention as a key regulator of serum triglyceride concentrations. An ApoA5 mouse knock-out model produced an approximately fourfold increase in serum triglycerides, whereas a knock-in model with human ApoA5 produced 50-70% lower concentrations of mouse serum triglycerides. In addition, peroxisome proliferator-activated receptor-
agonists, which are used clinically to lower serum triglyceride concentrations, cause increased ApoA5 mRNA expression. Despite these compelling molecular biology data, relatively little is known about ApoA5 protein in human serum.
Methods: To better understand circulating concentrations and lipoprotein particle distribution of ApoA5, we expressed the recombinant human ApoA5 protein and raised antibodies against both the NH2 and COOH termini.
Results: Using the above reagents, we demonstrate for the first time that ApoA5 is present in human serum, although at much lower concentrations than other apolipoproteins such as ApoA1. Using a dual-antibody sandwich ELISA that we developed, we observed ApoA5 concentrations in human serum ranging from 24 to 406 µg/L compared with 
1 g/L for ApoA1. We also examined the lipoprotein particle distribution of ApoA5 and found that ApoA5 was detectable in VLDL, HDL, and chylomicrons, but not LDL.
Conclusions: These data demonstrate for the first time that ApoA5 is a secreted protein present in human serum and is associated with specific lipoprotein particles. In addition, our data indicate that the circulating concentration of human ApoA5 is very low compared with other apolipoproteins.
The following articles in journals at HighWire Press have cited this article:
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 J. Kahri, J. Fruchart-Najib, N. Matikainen, J.-C. Fruchart, J. Vakkilainen, and M.-R. Taskinen The Increase of Apolipoprotein A-V During Postprandial Lipemia Parallels the Response of Triglyceride-Rich Lipoproteins in Type 2 Diabetes: No relationship between apoA-V and postheparin plasma lipolytic activity Diabetes Care, August 1, 2007; 30(8): 2083 - 2085. [Full Text] [PDF]
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A. Dichlberger, L. A. Cogburn, J. Nimpf, and W. J. Schneider Avian apolipoprotein A-V binds to LDL receptor gene family members J. Lipid Res., July 1, 2007; 48(7): 1451 - 1456. [Abstract] [Full Text] [PDF]
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S. Qu, G. Perdomo, D. Su, F. M. D'Souza, N. S. Shachter, and H. H. Dong Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice J. Lipid Res., July 1, 2007; 48(7): 1476 - 1487. [Abstract] [Full Text] [PDF]
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X. Shu, J. Chan, R. O. Ryan, and T. M. Forte Apolipoprotein A-V association with intracellular lipid droplets J. Lipid Res., July 1, 2007; 48(7): 1445 - 1450. [Abstract] [Full Text] [PDF]
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J. A. Beckstead, K. Wong, V. Gupta, C.-P. L. Wan, V. R. Cook, R. B. Weinberg, P. M. M. Weers, and R. O. Ryan The C Terminus of Apolipoprotein A-V Modulates Lipid-binding Activity J. Biol. Chem., May 25, 2007; 282(21): 15484 - 15489. [Abstract] [Full Text] [PDF]
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D. C. Chan, G. F. Watts, M. N. Nguyen, and P. H. R. Barrett Apolipoproteins C-III and A-V as Predictors of Very-Low-Density Lipoprotein Triglyceride and Apolipoprotein B-100 Kinetics Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 590 - 596. [Abstract] [Full Text] [PDF]
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M. Ishihara, T. Kujiraoka, T. Iwasaki, M. Nagano, M. Takano, J. Ishii, M. Tsuji, H. Ide, I. P. Miller, N. E. Miller, et al. A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V concentration J. Lipid Res., September 1, 2005; 46(9): 2015 - 2022. [Abstract] [Full Text] [PDF]
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A. E. Schultze, W. E. Alborn, R. K. Newton, and R. J. Konrad Administration of a PPAR{alpha} agonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/apolipoprotein C-III ratio J. Lipid Res., August 1, 2005; 46(8): 1591 - 1595. [Abstract] [Full Text] [PDF]
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