CoChat
Sign Up
Cited by 93

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression

Aryal, Binod, Rotllan, Noemi, Araldi, Elisa, Ramírez, Cristina M., He, Shun, Chousterman, Benjamin G., Fenn, Ashley M., Wanschel, Amarylis, Madrigal-Matute, Julio, Warrier, Nikhil, Martín-Ventura, Jose L., Swirski, Filip K., Suárez, Yajaira, Fernández-Hernando, Carlos·2016·Nature Communications
DOI 10.1038/ncomms12313PMC PMC4974469
Open this paper in CoChat — free account

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms12313

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

1 retracted

Flagged first, then by citations

Show all 6 references

Research works printed but not linked: 62

  1. Ross, R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999). · DOI · Paper page
  2. Glass, C. K. & Witztum, J. L. Atherosclerosis. The road ahead. Cell 104, 503–516 (2001). · DOI
  3. Weijenberg, M. P., Feskens, E. J. & Kromhout, D. White blood cell count and the risk of coronary heart disease and all-cause mortality in elderly men. Arterioscler. Thromb. Vasc. Biol. 16, 499–503 (1996). · DOI
  4. Averill, L. E., Meagher, R. C. & Gerrity, R. G. Enhanced monocyte progenitor cell proliferation in bone marrow of hyperlipemic swine. Am. J. Pathol. 135, 369–377 (1989).
  5. Feldman, D. L., Mogelesky, T. C., Liptak, B. F. & Gerrity, R. G. Leukocytosis in rabbits with diet-induced atherosclerosis. Arterioscler. Thromb. 11, 985–994 (1991). · DOI
  6. Yvan-Charvet, L. et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 328, 1689–1693 (2010). · DOI
  7. Swirski, F. K. et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J. Clin. Invest. 117, 195–205 (2007). · DOI
  8. Zhang, C. C. et al. Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells. Nat. Med. 12, 240–245 (2006). · DOI
  9. Zheng, J. et al. Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature 485, 656–660 (2012). · DOI
  10. Blank, U. et al. Angptl4 maintains in vivo repopulation capacity of CD34+ human cord blood cells. Eur. J. Haematol. 89, 198–205 (2012). · DOI
  11. Sukonina, V., Lookene, A., Olivecrona, T. & Olivecrona, G. Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue. Proc. Natl Acad. Sci. USA 103, 17450–17455 (2006). · DOI · Paper page
  12. Xu, A. et al. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. Proc. Natl Acad. Sci. USA 102, 6086–6091 (2005). · DOI · Paper page
  13. Gealekman, O. et al. Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production. Am. J. Physiol. Endocrinol. Metab. 295, E1056–E1064 (2008). · DOI
  14. Padua, D. et al. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133, 66–77 (2008). · DOI
  15. Goh, Y. Y. et al. Angiopoietin-like 4 interacts with integrins beta1 and beta5 to modulate keratinocyte migration. Am. J. Pathol. 177, 2791–2803 (2010). · DOI
  16. Yoshida, K., Shimizugawa, T., Ono, M. & Furukawa, H. Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase. J. Lipid. Res. 43, 1770–1772 (2002). · DOI · Paper page
  17. Mandard, S. et al. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity. J. Biol. Chem. 281, 934–944 (2006). · DOI · Paper page
  18. Romeo, S. et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat. Genet. 39, 513–516 (2007). · DOI · Paper page
  19. Talmud, P. J. et al. ANGPTL4 E40K and T266M: effects on plasma triglyceride and HDL levels, postprandial responses, and CHD risk. Arterioscler. Thromb. Vasc. Biol. 28, 2319–2325 (2008). · DOI · Paper page
  20. Yoon, J. C. et al. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol. Cell Biol. 20, 5343–5349 (2000). · DOI · Paper page
  21. Kersten, S. et al. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J. Biol. Chem. 275, 28488–28493 (2000). · DOI · Paper page
  22. Koliwad, S. K. et al. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor) is a direct glucocorticoid receptor target and participates in glucocorticoid-regulated triglyceride metabolism. J. Biol. Chem. 284, 25593–25601 (2009). · DOI · Paper page
  23. Belanger, A. J. et al. Hypoxia up-regulates expression of peroxisome proliferator-activated receptor gamma angiopoietin-related gene (PGAR) in cardiomyocytes: role of hypoxia inducible factor 1alpha. J. Mol. Cell. Cardiol. 34, 765–774 (2002). · DOI
  24. Lichtenstein, L. et al. Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages. Cell Metab. 12, 580–592 (2010). · DOI · Paper page
  25. Wilson, K., Fry, G. L., Chappell, D. A., Sigmund, C. D. & Medh, J. D. Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein e knockout mice but not in C57BL/6 mice. Arterioscler. Thromb. Vasc. Biol. 21, 1809–1815 (2001). · DOI
  26. Babaev, V. R. et al. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. J. Clin. Invest. 103, 1697–1705 (1999). · DOI · Paper page
  27. Adachi, H. et al. Angptl4 deficiency decreases serum triglyceride levels in low-density lipoprotein receptor knockout mice and streptozotocin-induced diabetic mice. Biochem. Biophys. Res. Commun. 409, 177–180 (2011). · DOI
  28. Georgiadi, A. et al. Overexpression of angiopoietin-like protein 4 protects against atherosclerosis development. Arterioscler. Thromb. Vasc. Biol. 33, 1529–1537 (2013). · DOI · Paper page
  29. Suzuki, H. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386, 292–296 (1997). · DOI
  30. Kunjathoor, V. V. et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 277, 49982–49988 (2002). · DOI
  31. Desvergne, B. & Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20, 649–688 (1999).
  32. Marsch, E., Sluimer, J. C. & Daemen, M. J. Hypoxia in atherosclerosis and inflammation. Curr. Opin. Lipidol. 24, 393–400 (2013). · DOI
  33. Lewis, J. S., Lee, J. A., Underwood, J. C., Harris, A. L. & Lewis, C. E. Macrophage responses to hypoxia: relevance to disease mechanisms. J. Leukoc. Biol. 66, 889–900 (1999). · DOI
  34. Murata, M. et al. Hypoxia upregulates the expression of angiopoietin-like-4 in human articular chondrocytes: role of angiopoietin-like-4 in the expression of matrix metalloproteinases and cartilage degradation. J. Orthop. Res. 27, 50–57 (2009). · DOI
  35. Li, H. et al. Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin beta1 signaling in human hepatocellular carcinoma. Hepatology 54, 910–919 (2011). · DOI
  36. Adachi, H. et al. Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis. Biochem. Biophys. Res. Commun. 379, 806–811 (2009). · DOI
  37. Desai, U. et al. Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice. Proc. Natl Acad. Sci. USA 104, 11766–11771 (2007). · DOI · Paper page
  38. Falk, E., Shah, P. K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995). · DOI · Paper page
  39. Kolodgie, F. D. et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 90, 1385–1391 (2004). · DOI
  40. Robbins, C. S. et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19, 1166–1172 (2013). · DOI · Paper page
  41. Newby, A. C. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler. Thromb. Vasc. Biol. 28, 2108–2114 (2008). · DOI · Paper page
  42. Tall, A. R., Yvan-Charvet, L., Westerterp, M. & Murphy, A. J. Cholesterol efflux: a novel regulator of myelopoiesis and atherogenesis. Arterioscler. Thromb. Vasc. Biol. 32, 2547–2552 (2012). · DOI
  43. Soehnlein, O. & Swirski, F. K. Hypercholesterolemia links hematopoiesis with atherosclerosis. Trends Endocrinol. Metab. 24, 129–136 (2013). · DOI
  44. Jahn, T., Leifheit, E., Gooch, S., Sindhu, S. & Weinberg, K. Lipid rafts are required for Kit survival and proliferation signals. Blood 110, 1739–1747 (2007). · DOI
  45. Neufeld, E. B. et al. Cellular localization and trafficking of the human ABCA1 transporter. J. Biol. Chem. 276, 27584–27590 (2001). · DOI
  46. Tabas, I. Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. J. Clin. Invest. 110, 905–911 (2002). · DOI
  47. Kellner-Weibel, G. et al. Effects of intracellular free cholesterol accumulation on macrophage viability: a model for foam cell death. Arterioscler. Thromb. Vasc. Biol. 18, 423–431 (1998). · DOI
  48. Leitinger, N. & Schulman, I. G. Phenotypic polarization of macrophages in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 33, 1120–1126 (2013). · DOI
  49. Bouhlel, M. A. et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 6, 137–143 (2007). · DOI · Paper page
  50. Stoger, J. L. et al. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis 225, 461–468 (2012). · DOI
  51. Tedgui, A. & Mallat, Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol. Rev. 86, 515–581 (2006). · DOI
  52. Zhang, C. C., Kaba, M., Iizuka, S., Huynh, H. & Lodish, H. F. Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation. Blood 111, 3415–3423 (2008). · DOI
  53. Khoury, M. et al. Mesenchymal stem cells secreting angiopoietin-like-5 support efficient expansion of human hematopoietic stem cells without compromising their repopulating potential. Stem Cells Dev. 20, 1371–1381 (2011). · DOI
  54. Tacke, F. et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest. 117, 185–194 (2007). · DOI · Paper page
  55. Tontonoz, P., Nagy, L., Alvarez, J. G., Thomazy, V. A. & Evans, R. M. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93, 241–252 (1998). · DOI
  56. Merkel, M. et al. Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: direct evidence that lipoprotein lipase bridging occurs in vivo. Proc. Natl Acad. Sci. USA 95, 13841–13846 (1998). · DOI
  57. Babaev, V. R., Patel, M. B., Semenkovich, C. F., Fazio, S. & Linton, M. F. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. J. Biol. Chem. 275, 26293–26299 (2000). · DOI
  58. Gustafsson, M. et al. Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase. Circ. Res. 101, 777–783 (2007). · DOI
  59. Spann, N. J. et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151, 138–152 (2012). · DOI
  60. Wang, Y. & Oram, J. F. Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1. J. Biol. Chem. 277, 5692–5697 (2002). · DOI
  61. Rotllan, N. et al. Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis. FASEB J. 29, 597–610 (2015). · DOI
  62. Fazio, S. et al. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J. Clin. Invest. 107, 163–171 (2001). · DOI

Cited by

Sorted by citations

See all 93

Metadata

Authors
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.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-07-27
Volume
7
Issue
1
ISSN
2041-1723
DOI
10.1038/ncomms12313
PMC
PMC4974469
Cited by
93
References
6
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review