Protective Role of Apelin in a Mouse Model of Post-Intensive Care Syndrome.

Summary

In a combined lung injury–immobilization mouse model, impaired Apelin-APJ signaling drove PICS-like muscle, lung, and neurobehavioral changes; Apelin overexpression ameliorated these phenotypes and lowered systemic IL-6. In severe COVID-19 ARDS survivors, ICU-acquired weakness correlated with low plasma Apelin and elevated IL-6, with PBMC transcriptomes echoing neuroinflammation and depression signatures.

Key Findings

• Apelin-APJ signaling was downregulated in skeletal muscle and its deficiency exacerbated PICS-like phenotypes in mice.
• Muscle-specific Apelin overexpression reduced systemic IL-6, restored circulating Apelin, and mitigated muscle, lung, and neurobehavioral impairments.
• In severe COVID-19 ARDS survivors, ICU-acquired weakness was associated with low plasma Apelin and elevated IL-6; PBMC transcriptomes reflected depression and neurodegeneration signatures.

Clinical Implications

Apelin-APJ signaling could serve as a biomarker and therapeutic target to reduce long-term physical and neuropsychiatric sequelae after ARDS/COVID-19. Patient stratification by plasma Apelin/IL-6 may guide future interventional trials.

Limitations

• Animal model may not fully recapitulate the complexity of human PICS and ARDS recovery
• Human data are observational with limited sample details, precluding causal inference and tissue-specific attribution

Future Directions

Define tissue-specific roles of Apelin-APJ, validate plasma Apelin/IL-6 as biomarkers, and test Apelin-modulating therapies in preclinical and early-phase clinical trials.