TY - EJOU
AU - Ren, Zhuyuan
AU - Chen, Yong
AU - Wu, Jiaqiao
AU - Li, Qiang
AU - Fu, Qiang
TI - Sevoflurane-Induced Pulmonary Microvascular Hyperpermeability via Upregulating EGR2
T2 - BIOCELL
PY -
VL -
IS -
SN - 1667-5746
AB - Background: Volatile anesthetics such as sevoflurane are ubiquitous in perioperative care, yet their unintended consequences on pulmonary microvascular integrity and the upstream intracellular signaling pathways remain incompletely defined. This study elucidates the precise transcriptional mechanisms linking sevoflurane exposure to pulmonary endothelial hyperpermeability. Methods: Transendothelial electrical resistance (TEER) and macromolecular permeability were dynamically quantified in human pulmonary microvascular endothelial cell (HPMEC) monolayers following sevoflurane exposure. Global transcriptomic profiling (RNA-seq) was employed to identify core regulatory nodes, which were functionally validated via targeted siRNA silencing in vitro and subsequently corroborated in a murine model of clinical sevoflurane inhalation. Results: Sevoflurane (0.2–0.3 mM) induced a dose- and time-dependent disruption of endothelial barrier function, evidenced by a up to 2.5-fold increase in macromolecular permeability (p < 0.001) and a 64% reduction in transendothelial electrical resistance (TEER, dropping from ~28 to ~10 Ω·cm2; p < 0.001). Unbiased transcriptomic analysis identified Early Growth Response 2 (EGR2) as the principal transcriptional driver. Sevoflurane provoked a 1.9-fold increase in EGR2 mRNA transcription (p < 0.01) and a >10-fold surge in its nuclear accumulation (p < 0.01), triggering profound downstream secretion of Vascular Endothelial Growth Factor (VEGF). Crucially, targeted knockdown of EGR2 abolished the sevoflurane-induced VEGF surge and fully preserved barrier integrity, restoring TEER and permeability to baseline control levels (p < 0.001 vs. sevoflurane alone). In vivo assessments confirmed that 3.3% sevoflurane inhalation significantly upregulates the pulmonary EGR2/VEGF axis, resulting in overt microvascular leakage and interstitial edema. Conclusion: Sevoflurane compromises pulmonary microvascular endothelium via the aberrant activation of the EGR2/VEGF signaling axis. Inhibiting EGR2 represents a novel, targeted therapeutic strategy to preserve vascular integrity and mitigate anesthetic-induced lung injury in susceptible surgical populations.
KW - Sevoflurane; pulmonary microvascular endothelium; vascular permeability; early growth response 2 (EGR2); vascular endothelial growth factor (VEGF); perioperative lung injury
DO - 10.32604/biocell.2026.085300