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

Schaap, FG; Nierman, MC; Berbee, JFP; Hattori, H; Talmud, PJ; Vaessen, SFC; ... Groen, AK; + view all (2006) Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia. J LIPID RES , 47 (10) 2333 - 2339. 10.1194/jlr.M500533-JLR200. Gold open access

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 hyper-lipidemia, 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 = 10.09, 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).jlr 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. - Schaap, F. G., M. C. Nierman, J. F. P. Berbee, H. Hattori, P. J. Talmud, S. F. C. Vaessen, P. C. N. Rensen, R.A.F.M. Chamuleau, J. A. Kuivenhoven, and A. K. Groen. Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia.

Type:Article
Title:Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia
Open access status:An open access publication
DOI:10.1194/jlr.M500533-JLR200
Keywords:apolipoprotein C-III, apolipoprotein A-V, lipoprotein lipase, enzyme-linked immunosorbent assay, APOLIPOPROTEIN-A-V, PLASMA TRIGLYCERIDE LEVELS, ACTIVATED RECEPTOR-ALPHA, LIPOPROTEIN-LIPASE, RICH LIPOPROTEINS, RESPONSE ELEMENT, GENE-CLUSTER, MICE, HYDROLYSIS, METABOLISM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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