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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. t-shoji@med.osaka-cu.ac.jp

    , , , , , , , ,

    Source

    Atherosclerosis 207:2 2009 Dec pg 579-84

    MeSH

    Angiopoietin-like Proteins
    Angiopoietins
    Biomarkers
    Case-Control Studies
    Cross-Sectional Studies
    Down-Regulation
    Dyslipidemias
    Enzyme-Linked Immunosorbent Assay
    Female
    Humans
    Kidney Failure, Chronic
    Lipoproteins
    Male
    Middle Aged
    Regression Analysis
    Renal Dialysis
    Risk Assessment
    Risk Factors
    Ultracentrifugation
    Uremia

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    19540497

    Citation

    Shoji, Tetsuo, et al. "Plasma Angiopoietin-like Protein 3 (ANGPTL3) Concentration Is Associated With Uremic Dyslipidemia." Atherosclerosis, vol. 207, no. 2, 2009, pp. 579-84.
    Shoji T, Hatsuda S, Tsuchikura S, et al. Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia. Atherosclerosis. 2009;207(2):579-84.
    Shoji, T., Hatsuda, S., Tsuchikura, S., Kimoto, E., Kakiya, R., Tahara, H., ... Nishizawa, Y. (2009). Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia. Atherosclerosis, 207(2), pp. 579-84. doi:10.1016/j.atherosclerosis.2009.05.023.
    Shoji T, et al. Plasma Angiopoietin-like Protein 3 (ANGPTL3) Concentration Is Associated With Uremic Dyslipidemia. Atherosclerosis. 2009;207(2):579-84. PubMed PMID: 19540497.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Plasma angiopoietin-like protein 3 (ANGPTL3) concentration is associated with uremic dyslipidemia. AU - Shoji,Tetsuo, AU - Hatsuda,Sawako, AU - Tsuchikura,Shoko, AU - Kimoto,Eiji, AU - Kakiya,Ryusuke, AU - Tahara,Hideki, AU - Koyama,Hidenori, AU - Emoto,Masanori, AU - Tabata,Tsutomu, AU - Nishizawa,Yoshiki, Y1 - 2009/05/27/ PY - 2009/01/08/received PY - 2009/05/17/revised PY - 2009/05/20/accepted PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2010/1/29/medline SP - 579 EP - 84 JF - Atherosclerosis JO - Atherosclerosis VL - 207 IS - 2 N2 - 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. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/19540497/Plasma_angiopoietin_like_protein_3__ANGPTL3__concentration_is_associated_with_uremic_dyslipidemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(09)00416-X DB - PRIME DP - Unbound Medicine ER -