Open Access

ARTICLE

Sevoflurane-Induced Pulmonary Microvascular Hyperpermeability via Upregulating EGR2

Zhuyuan Ren, Yong Chen, Jiaqiao Wu, Qiang Li, Qiang Fu^*

Department of Anesthesiology, the Third People’s Hospital of Chengdu, Chengdu, China

* Corresponding Author: Qiang Fu. Email:

BIOCELL 2026, 50(10), 12 https://doi.org/10.32604/biocell.2026.085300

Received 08 May 2026; Accepted 23 June 2026; Issue published 22 September 2026

Abstract

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.

---

Keywords

---

Supplementary Material

Supplementary Material File

---