Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Shoji, T. et al.

Tetsuo Shoji, Sawako Hatsuda, Shoko Tsuchikura, Eiji Kimoto, Ryusuke Kakiya, Hideki Tahara, Hidenori Koyama, Masanori Emoto, Tsutomu Tabata, Yoshiki Nishizawa,

Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia.

OBJECTIVE: Angiopoietin-like protein 3, a liver-derived plasma protein, increases plasma triglycerides (TG) in mice by suppressing the activity of lipoprotein lipase, a key enzyme in plasma TG clearance. Uremic dyslipidemia is characterized by increased TG-rich lipoproteins such as very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), lowered high-density lipoprotein (HDL), and TG-enrichment of low-density lipoprotein (LDL) and HDL. Since the role of angiopoietin-like protein 3 (ANGPTL3) in uremic dyslipidemia is unknown, we examined its possible association with the lipoprotein abnormalities in patients with chronic renal failure (CRF). METHODS: The subjects were 202 hemodialysis patients, 44 predialysis patients with CRF and 148 healthy control subjects comparable in age and sex. Fasting plasma ANGPTL3 was measured by enzyme-linked immunoassay, and lipoproteins were fractioned by ultracentrifugation. RESULTS: Median (25th-75th percentile range) ANGPTL3 levels were 523 (409-645) and 393 (308-511)ng/mL in hemodialysis and predialysis patients, respectively, which were significantly lower than the control level of 700 (570-875)ng/mL. In the total subjects, ANGPTL3 was inversely correlated with VLDL- and IDL-cholesterol levels, and positively with HDL-cholesterol. ANGPTL3 correlated inversely with TG/cholesterol ratios of both LDL and HDL. In multiple regression models, these associations, excluding TG/cholesterol ratio of LDL, remained significant and independent of possible confounders including age, sex, body mass index, insulin resistance index (HOMA-IR), and adiponectin, whereas the associations of ANGPTL3 with the lipoprotein parameters were less significant when apoC-II/C-III ratio was included in the models. CONCLUSION: The reduced ANGPTL3 level in hemodialysis patients was consistently associated with the major components of uremic dyslipidemia. ANGPTL3 may be a novel factor contributing to uremic dyslipidemia.[1]

References

Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia. Shoji, T., Hatsuda, S., Tsuchikura, S., Kimoto, E., Kakiya, R., Tahara, H., Koyama, H., Emoto, M., Tabata, T., Nishizawa, Y. Atherosclerosis (2009) [Pubmed]

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