Macrophage Autophagy Plays a Protective Role in Advanced Atherosclerosis
By Xianghai Liao, J. Sluimer, Ying C Wang, Manikandan Subramanian, K. Brown, J. S. Pattison, J. Robbins, Jennifer Martinez, I. Tabas. Cell Metabolism, 2012
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SUMMARY 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 pro-apoptotic 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.
Subfields: Epidemiology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7de6998063a2df4747c4273bb41e4401fa4879ba
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Citations in the corpus
- The immune response in tuberculosis. (2013, background): “tuberculosis–infected macrophages are themselves rapidly engulfed by uninfected macrophages through a process called efferocytosis (140) (Figure 4), generally regarded as a constitutive housekeeping function of macrophages.”
- Vascular complications of diabetes: mechanisms of injury and protective factors (2013, background): “Macrophage autophagy also prevents apoptosis and promotes efferocytosis of apoptotic macrophages (Liao et al., 2012).”
- Macrophage Phenotype and Function in Different Stages of Atherosclerosis (2016, unknown): “For example, inhibition of autophagy by silencing the E3 ubiquitin ligase ATG5 (autophagy protein 5) results in increased macrophage apoptosis and NADPH oxidase–mediated oxidative stress and, in addition, renders the apoptotic cells less well recognized by efferocytes.(123) Furthermore, defective au”