Macrophage autophagy plays a protective role in advanced atherosclerosis

Xianghai Liao, Judith C. Sluimer, Ying Wang, Manikandan Subramanian, Kristy Brown, James S Pattison, Jeffrey Robbins, Jennifer Martinez, Ira Tabas

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

In advanced atherosclerosis, macrophage apoptosis coupled with defective phagocytic clearance of the apoptotic cells (efferocytosis) promotes plaque necrosis, which precipitates acute atherothrombotic cardiovascular events. Oxidative and endoplasmic reticulum (ER) stress in macrophages are important causes of advanced lesional macrophage apoptosis. We now show that proapoptotic oxidative/ER stress inducers trigger another stress reaction in macrophages, autophagy. Inhibition of autophagy by silencing ATG5 or other autophagy mediators enhances apoptosis and NADPH oxidase-mediated oxidative stress while at the same time rendering the apoptotic cells less well recognized by efferocytes. Most importantly, macrophage ATG5 deficiency in fat-fed Ldlr -/- mice increases apoptosis and oxidative stress in advanced lesional macrophages, promotes plaque necrosis, and worsens lesional efferocytosis. These findings reveal a protective process in oxidatively stressed macrophages relevant to plaque necrosis, suggesting a mechanism-based strategy to therapeutically suppress atherosclerosis progression and its clinical sequelae.

Original languageEnglish (US)
Pages (from-to)545-553
Number of pages9
JournalCell Metabolism
Volume15
Issue number4
DOIs
StatePublished - Apr 4 2012
Externally publishedYes

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Autophagy
Atherosclerosis
Macrophages
Apoptosis
Endoplasmic Reticulum Stress
Necrosis
Oxidative Stress
NADPH Oxidase
Fats

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Liao, X., Sluimer, J. C., Wang, Y., Subramanian, M., Brown, K., Pattison, J. S., ... Tabas, I. (2012). Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metabolism, 15(4), 545-553. https://doi.org/10.1016/j.cmet.2012.01.022

Macrophage autophagy plays a protective role in advanced atherosclerosis. / Liao, Xianghai; Sluimer, Judith C.; Wang, Ying; Subramanian, Manikandan; Brown, Kristy; Pattison, James S; Robbins, Jeffrey; Martinez, Jennifer; Tabas, Ira.

In: Cell Metabolism, Vol. 15, No. 4, 04.04.2012, p. 545-553.

Research output: Contribution to journalArticle

Liao, X, Sluimer, JC, Wang, Y, Subramanian, M, Brown, K, Pattison, JS, Robbins, J, Martinez, J & Tabas, I 2012, 'Macrophage autophagy plays a protective role in advanced atherosclerosis', Cell Metabolism, vol. 15, no. 4, pp. 545-553. https://doi.org/10.1016/j.cmet.2012.01.022
Liao, Xianghai ; Sluimer, Judith C. ; Wang, Ying ; Subramanian, Manikandan ; Brown, Kristy ; Pattison, James S ; Robbins, Jeffrey ; Martinez, Jennifer ; Tabas, Ira. / Macrophage autophagy plays a protective role in advanced atherosclerosis. In: Cell Metabolism. 2012 ; Vol. 15, No. 4. pp. 545-553.
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