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Journal of Lipid Research, Vol. 47, 2333-2339, October 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia

Frank G. Schaap^1,*, Melchior C. Nierman, Jimmy F. P. Berbée, Hiroaki Hattori^**, Philippa J. Talmud, Stefan F. C. Vaessen, Patrick C. N. Rensen, Robert A. F. M. Chamuleau^*, Jan Albert Kuivenhoven and Albert K. Groen^*,

^* Academic Medical Center Liver Center, 1105 BK Amsterdam, The Netherlands
Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
Department of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
^** Department of Advanced Medical Technology and Development, BML, Inc., Kawagoe, Saitama 350-1101, Japan
Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JF, UK
Department of Medical Biochemistry, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

Published, JLR Papers in Press, July 21, 2006.

¹ To whom correspondence should be addressed. e-mail: f.g.schaap{at}amc.uva.nl

ABSTRACT

The relevance of apolipoprotein A-V (apoA-V) for human lipid homeostasis is underscored by genetic association studies and the identification of truncation-causing mutations in the APOA5 gene as a cause of type V hyperlipidemia, compatible with an LPL-activating role of apoA-V. An inverse correlation between plasma apoA-V and triglyceride (TG) levels has been surmised from animal data. Recent studies in human subjects using (semi)quantitative immunoassays, however, do not provide unambiguous support for such a relationship. Here, we used a novel, validated ELISA to measure plasma apoA-V levels in patients (n = 28) with hypertriglyceridemia (HTG; 1.8–78.7 mmol TG/l) and normolipidemic controls (n = 42). Unexpectedly, plasma apoA-V levels were markedly increased in the HTG subjects compared with controls (1,987 vs. 258 ng/ml; P < 0.001). In the HTG group, apoA-V and TG were positively correlated (r = +0.44, P = 0.02). In addition, we noted an increased level of the LPL-inhibitory protein apoC-III in the HTG group (45.8 vs. 10.6 mg/dl in controls; P < 0.001). The correlation between apoA-V and TG levels in the HTG group disappeared (partial r = +0.09, P = 0.65) when controlling for apoC-III levels. In contrast, apoC-III and TG remained positively correlated in this group when controlling for apoA-V (partial r = +0.43, P = 0.025). Our findings suggest that in HTG patients, increased TG levels are accompanied by high plasma levels of apoA-V and apoC-III, apolipoproteins with opposite modes of action. This study provides evidence for a complex interaction between apoA-V and apoC-III in patients with severe HTG.

Supplementary key words apolipoprotein C-III • apolipoprotein A-V • lipoprotein lipase • enzyme-linked immunosorbent assay

Abbreviations: apoA-V, apolipoprotein A-V; HTG, hypertriglyceridemia, hypertriglyceridemic; MAb, monoclonal antibody; TC, total cholesterol; TG, triglyceride

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