CGRP alleviates lipopolysaccharide-induced ARDS inflammation via the HIF-1α signaling pathway.

Summary

CGRP levels are elevated in ARDS and the peptide mitigates LPS-induced lung injury by shifting macrophage polarization (↓M1, ↑M2) via its receptor RAMP1. Transcriptomics implicate HIF-1α; CGRP alleviates pathological injury, inflammation, and oxidative stress by inhibiting the HIF-1α pathway.

Key Findings

• CGRP expression is increased in ARDS patient serum and in vitro/in vivo ARDS models.
• CGRP, via RAMP1, decreases M1 and increases M2 macrophages, reducing injury, inflammation, oxidative stress, and apoptosis in LPS-induced ARDS.
• Transcriptomics implicate HIF-1α; CGRP alleviates damage by inhibiting the HIF-1α pathway.

Clinical Implications

Supports exploration of CGRP pathway modulators to treat ARDS-related inflammatory surges and guides biomarker-driven strategies focused on macrophage polarization and HIF-1α.

Limitations

• Preclinical nature limits direct clinical generalizability
• Model primarily based on LPS-induced injury; human interventional data lacking

Future Directions

Evaluate CGRP agonists/antagonists and HIF-1α modulators in clinically relevant ARDS models and early-phase human trials with macrophage polarization biomarkers.