ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression

Binod Aryal, Noemi Rotllan, Elisa Araldi, Cristina M. Ramírez, Shun He, Benjamin G. Chousterman, Ashley M. Fenn, Amarylis Wanschel, Julio Madrigal-Matute, Nikhil Warrier, Jose L. Martín-Ventura, Filip K. Swirski, Yajaira Suárez, Carlos Fernández-Hernando

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28 Scopus citations

Abstract

Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

Original languageEnglish (US)
Article number12313
JournalNature communications
Volume7
DOIs
StatePublished - Jul 27 2016

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Aryal, B., Rotllan, N., Araldi, E., Ramírez, C. M., He, S., Chousterman, B. G., Fenn, A. M., Wanschel, A., Madrigal-Matute, J., Warrier, N., Martín-Ventura, J. L., Swirski, F. K., Suárez, Y., & Fernández-Hernando, C. (2016). ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature communications, 7, [12313]. https://doi.org/10.1038/ncomms12313