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Autophagy links inflammasomes to atherosclerotic progression.

Publication ,  Journal Article
Razani, B; Feng, C; Coleman, T; Emanuel, R; Wen, H; Hwang, S; Ting, JP; Virgin, HW; Kastan, MB; Semenkovich, CF
Published in: Cell Metab
April 4, 2012

We investigated the role of autophagy in atherosclerosis. During plaque formation in mice, autophagic markers colocalized predominantly with macrophages (mφ). Atherosclerotic aortas had elevated levels of p62, suggesting that dysfunctional autophagy is characteristic of plaques. To determine whether autophagy directly influences atherogenesis, we characterized Beclin-1 heterozygous-null and mφ-specific ATG5-null (ATG5-mφKO) mice, commonly used models of autophagy haploinsufficiency and deficiency, respectively. Haploinsufficent Beclin-1 mice had no atherosclerotic phenotype, but ATG5-mφKO mice had increased plaques, suggesting an essential role for basal levels of autophagy in atheroprotection. Defective autophagy is associated with proatherogenic inflammasome activation. Classic inflammasome markers were robustly induced in ATG5-null mφ, especially when coincubated with cholesterol crystals. Moreover, cholesterol crystals appear to be increased in ATG5-mφKO plaques, suggesting a potentially vicious cycle of crystal formation and inflammasome activation in autophagy-deficient plaques. These results show that autophagy becomes dysfunctional in atherosclerosis and its deficiency promotes atherosclerosis in part through inflammasome hyperactivation.

Duke Scholars

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 4, 2012

Volume

15

Issue

4

Start / End Page

534 / 544

Location

United States

Related Subject Headings

  • Plaque, Atherosclerotic
  • Models, Biological
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Macrophage Activation
  • Inflammation
  • Inflammasomes
  • Heterozygote
 

Citation

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Razani, B., Feng, C., Coleman, T., Emanuel, R., Wen, H., Hwang, S., … Semenkovich, C. F. (2012). Autophagy links inflammasomes to atherosclerotic progression. Cell Metab, 15(4), 534–544. https://doi.org/10.1016/j.cmet.2012.02.011
Razani, Babak, Chu Feng, Trey Coleman, Roy Emanuel, Haitao Wen, Seungmin Hwang, Jenny P. Ting, Herbert W. Virgin, Michael B. Kastan, and Clay F. Semenkovich. “Autophagy links inflammasomes to atherosclerotic progression.Cell Metab 15, no. 4 (April 4, 2012): 534–44. https://doi.org/10.1016/j.cmet.2012.02.011.
Razani B, Feng C, Coleman T, Emanuel R, Wen H, Hwang S, et al. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab. 2012 Apr 4;15(4):534–44.
Razani, Babak, et al. “Autophagy links inflammasomes to atherosclerotic progression.Cell Metab, vol. 15, no. 4, Apr. 2012, pp. 534–44. Pubmed, doi:10.1016/j.cmet.2012.02.011.
Razani B, Feng C, Coleman T, Emanuel R, Wen H, Hwang S, Ting JP, Virgin HW, Kastan MB, Semenkovich CF. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab. 2012 Apr 4;15(4):534–544.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 4, 2012

Volume

15

Issue

4

Start / End Page

534 / 544

Location

United States

Related Subject Headings

  • Plaque, Atherosclerotic
  • Models, Biological
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Macrophage Activation
  • Inflammation
  • Inflammasomes
  • Heterozygote