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Cardiovascular endocrinology

Is ANGPTL3 the next PCSK9?

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Recent reports suggest that molecular therapies targeting ANGPTL3 and its encoded protein angiopoietin-like protein 3 have clinical potential comparable to therapies targeting PCSK9 and its encoded protein proprotein convertase subtilisin/kexin type 9. By mainly affecting triglyceride-rich lipoproteins, ANGPTL3 inhibition might prove complementary to LDL cholesterol lowering with PCSK9 blockade.

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References

  1. Natarajan, P. & Kathiresan, S. PCSK9 inhibitors. Cell 165, 1037 (2016).

    Article  CAS  Google Scholar 

  2. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376, 1713–1722 (2017).

    Article  CAS  Google Scholar 

  3. Koishi, R. et al. Angptl3 regulates lipid metabolism in mice. Nat. Genet. 30, 151–157 (2002).

    Article  CAS  Google Scholar 

  4. Romeo, S. et al. Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans. J. Clin. Invest. 119, 70–79 (2009).

    CAS  PubMed  Google Scholar 

  5. Musunuru, K. et al. Exome sequencing. ANGPTL3 mutations, and familial combined hypolipidemia. N. Engl. J. Med. 363, 2220–2227 (2010).

    Article  CAS  Google Scholar 

  6. Teslovich, T. M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713 (2010).

    Article  CAS  Google Scholar 

  7. Pashos, E. E. et al. Large, diverse population cohorts of hiPSCs and derived hepatocyte-like cells reveal functional genetic variation at blood lipid-associated loci. Cell Stem Cell 20, 558–570.e10 (2017).

    Article  CAS  Google Scholar 

  8. Dewey, F. E. et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1612790 (2017).

  9. Graham, M. J. et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1701329 (2017).

  10. Stitziel, N. O. et al. ANGPTL3 deficiency and protection against coronary artery disease. J. Am. Coll. Cardiol. 69, 2054–2063 (2017).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, 11–104 SCTR, Philadelphia, 19104, Pennsylvania, USA

    Kiran Musunuru

  2. Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5.830, Boston, Massachusetts 02114, USA; and at the Program in Medical and Population Genetics, Broad Institute, 75 Ames Street, Cambridge, Massachusetts 02142, USA.,

    Sekar Kathiresan

  3. and at the Program in Medical and Population Genetics, Broad Institute, 75 Ames Street, Cambridge, Massachusetts 02142, USA.,

    Sekar Kathiresan

Authors
  1. Kiran Musunuru
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  2. Sekar Kathiresan
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Correspondence to Sekar Kathiresan.

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Competing interests

S.K. serves on a scientific advisory board for Regeneron Genetics Center, New York, USA, and has received consulting fees from Ionis Pharmaceuticals, California, USA. K.M. declares no competing interests.

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Musunuru, K., Kathiresan, S. Is ANGPTL3 the next PCSK9?. Nat Rev Endocrinol 13, 503–504 (2017). https://doi.org/10.1038/nrendo.2017.88

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