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Cited by 175

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice

Desai, Urvi, Lee, E-Chiang, Chung, Kyu, Gao, Cuihua, Gay, Jason, Key, Billie, Hansen, Gwenn, Machajewski, Dennis, Platt, Kenneth A., Sands, Arthur T., Schneider, Matthias, Van Sligtenhorst, Isaac, Suwanichkul, Adisak, Vogel, Peter, Wilganowski, Nat, Wingert, June, Zambrowicz, Brian P., Landes, Greg, Powell, David R.·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0705041104
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Abstract

We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 −/− mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL production and had modestly lower cholesterol levels. Also, both Angptl4 −/− suckling mice and adult mice fed a high-fat diet showed reduced viability associated with lipogranulomatous lesions of the intestines and their draining lymphatics and mesenteric lymph nodes. Treating C57BL/6J, ApoE −/−, LDLr −/−, and db/db mice with the anti-Angptl4 mAb 14D12 recapitulated the lipid and histopathologic phenotypes noted in Angptl4 −/− mice. This demonstrates that the knockout phenotype reflects not only the physiologic function of the Angptl4 gene but also predicts the pharmacologic consequences of Angptl4 protein inhibition with a neutralizing antibody in relevant models of human disease.

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  • Targeting ANGPTL3, ANGPTL4, or ANGPTL8 with antibodies or antisense oligos can lower plasma triglycerides in preclinical studies.

    “Preclinical studies using antibodies or antisense oligos showed that targeting ANGPTL3, ANGPTL4, or ANGPTL8 can lower plasma triglycerides (29, 56, 60, 165, 168–172).”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [29]

  • Targeting ANGPTL4 with an anti-ANGPTL4 antibody in mice fed a high-fat diet led to intestinal abnormalities, chylous ascites, lymph node inflammation, and premature death.

    “Unfortunately, targeting ANGPTL4 with an anti-ANGPTL4 antibody in mice fed a high-fat diet led to intestinal abnormalities, chylous ascites, lymph node inflammation, and premature death (29)”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [29]

  • In adipocytes, ANGPTL4 appears able to inactivate LPL both intracellularly and extracellularly.

    “In adipocytes, ANGPTL4 appears able to inactivate LPL both intracellularly (64, 65) and extracellularly (29, 66).”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [29]

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Citations

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Research works printed but not linked: 29

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Metadata

Authors
Desai, U., Lee, E.-C., Chung, K., Gao, C., Gay, J., Key, B., Hansen, G., Machajewski, D., Platt, K. A., Sands, A. T., Schneider, M., Van Sligtenhorst, I., Suwanichkul, A., Vogel, P., Wilganowski, N., Wingert, J., Zambrowicz, B. P., Landes, G., & Powell, D. R.
Affiliations
  • Departments of *Pharmaceutical Biology,
  • Biotherapeutics, and
  • Genetics, Lexicon Pharmaceuticals, Inc., 8800 Technology Forest Place, The Woodlands, TX, 77381
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-07-10
Volume
104
Issue
28
Pages
11766-11771
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0705041104
Cited by
175
References
1
Language
en

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