Autophagy and Inflammation in Cardiothoracic Surgery: The Mechanisms of Perioperative Lung Injury and Therapeutic Opportunities.
- 1Department of Thoracic Surgery, General Hospital of Southern Theater Command, Guangzhou, 510010, People's Republic of China.
Abstract
Autophagy is a lysosome-dependent stress-response pathway that maintains cellular homeostasis through the degradation and recycling of damaged proteins, dysfunctional organelles, and other cytoplasmic components. In the lung, autophagy is closely linked to inflammatory signaling, mitochondrial quality control, oxidative stress, epithelial barrier integrity, and immune-cell activation. These processes are highly relevant to respiratory diseases and perioperative pulmonary injury because hypoxia, mechanical stretch, ischemia-reperfusion, hyperoxia, infection-related stress, and systemic inflammation may alter autophagic flux. Context-dependent autophagic responses may protect lung tissue by limiting mitochondrial damage and excessive inflammatory activation, whereas impaired pathway completion may promote persistent reactive oxygen species production, endothelial and epithelial injury, fibroblast activation, and maladaptive tissue remodeling. In cardiothoracic surgery, lung resection, one-lung ventilation, cardiopulmonary bypass, and transplantation are clinically relevant settings in which autophagy-inflammation crosstalk may affect postoperative pulmonary complications and organ recovery. Here, we present a perioperative, flux-centered framework that distinguishes stress-induced initiation from autophagosome-lysosome fusion and lysosomal degradation. The framework integrates AMPK-mTORC1-ULK1 signaling with TFEB-dependent lysosomal biogenesis, FOXO transcriptional control, selective mitophagy, and downstream NLRP3, NF-κB, and cytokine responses. Human studies demonstrate biological heterogeneity but rarely measure dynamic flux; LC3-II, p62/SQSTM1, Beclin-1, or ATG abundance alone cannot establish pathway completion. Translational studies should use serial, compartment-aware autophagy-lysosome, mitochondrial-injury, and inflammatory readouts linked to standardized pulmonary outcomes. Major priorities include cell-resolved perioperative phenotyping, harmonized reporting of flux uncertainty, prospective one-lung-ventilation and cardiopulmonary-bypass cohorts, and short, mechanism-matched intervention studies with explicit safety endpoints.
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BibTeX
@article{li2026autophagy,
title = {{Autophagy and Inflammation in Cardiothoracic Surgery: The Mechanisms of Perioperative Lung Injury and Therapeutic Opportunities.}},
author = {Shouzhuo Li and Ranran Zhu and Xiujuan Yao and Shiying Liu and Xueling Liu},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s621928},
url = {https://europepmc.org/article/MED/42921200},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Autophagy and Inflammation in Cardiothoracic Surgery: The Mechanisms of Perioperative Lung Injury and Therapeutic Opportunities.
AU - Shouzhuo Li
AU - Ranran Zhu
AU - Xiujuan Yao
AU - Shiying Liu
AU - Xueling Liu
PY - 2026
DA - 2026/10/19
JO - Journal of inflammation research
DO - 10.2147/jir.s621928
UR - https://europepmc.org/article/MED/42921200
AB - Autophagy is a lysosome-dependent stress-response pathway that maintains cellular homeostasis through the degradation and recycling of damaged proteins, dysfunctional organelles, and other cytoplasmic components. In the lung, autophagy is closely linked to inflammatory signaling, mitochondrial quality control, oxidative stress, epithelial barrier integrity, and immune-cell activation. These processes are highly relevant to respiratory diseases and perioperative pulmonary injury because hypoxia, mechanical stretch, ischemia-reperfusion, hyperoxia, infection-related stress, and systemic inflammation may alter autophagic flux. Context-dependent autophagic responses may protect lung tissue by limiting mitochondrial damage and excessive inflammatory activation, whereas impaired pathway completion may promote persistent reactive oxygen species production, endothelial and epithelial injury, fibroblast activation, and maladaptive tissue remodeling. In cardiothoracic surgery, lung resection, one-lung ventilation, cardiopulmonary bypass, and transplantation are clinically relevant settings in which autophagy-inflammation crosstalk may affect postoperative pulmonary complications and organ recovery. Here, we present a perioperative, flux-centered framework that distinguishes stress-induced initiation from autophagosome-lysosome fusion and lysosomal degradation. The framework integrates AMPK-mTORC1-ULK1 signaling with TFEB-dependent lysosomal biogenesis, FOXO transcriptional control, selective mitophagy, and downstream NLRP3, NF-κB, and cytokine responses. Human studies demonstrate biological heterogeneity but rarely measure dynamic flux; LC3-II, p62/SQSTM1, Beclin-1, or ATG abundance alone cannot establish pathway completion. Translational studies should use serial, compartment-aware autophagy-lysosome, mitochondrial-injury, and inflammatory readouts linked to standardized pulmonary outcomes. Major priorities include cell-resolved perioperative phenotyping, harmonized reporting of flux uncertainty, prospective one-lung-ventilation and cardiopulmonary-bypass cohorts, and short, mechanism-matched intervention studies with explicit safety endpoints.
SN - 1178-7031
ER -