Unfractionated Heparin Attenuates Histone-Induced Pulmonary Endothelial Glycocalyx Injury: A Preliminary Study on the Roles of the ROCK Pathway and Heparanase‑1
- J Inflamm Res. 2026 Jun 8:19:573499. doi: 10.2147/JIR.S573499.
- 1. Department of Critical Care Medicine, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, People's Republic of China.
Purpose: This study aims to investigate the role of the Rho-associated kinase (ROCK)-1 pathway, with the involvement of heparanase (HPA)-1, in histone-induced disruption of the endothelial glycocalyx and the protective effects of unfractionated heparin (UFH).
Methods: Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro and divided into 4 groups: control group, histone group, histone+UFH group, and histone+ROCK inhibitor (Y27632) group. The control group was treated with phosphate buffer solution (PBS). Histone group was treated with histone 50μg/mL for 1 hour. UFH 10 IU/mL and Y27632 10 uM were added 30 min before exposure to histones.
Results: UFH attenuated histone-induced permeability changes of HPMECs. UFH reduced histone-induced syndecan-1 shedding and the depolymerization of Ace-tubulin and β-tubulin. UFH inhibited histone-induced decrease in syndecan-1 and Ace-tubulin. UFH inhibited histone-induced expression, re-distribution and secretion of HPA-1. UFH reduced histone-induced expression of ROCK-1 and phosphorylated Myosin light-chain (p-MLC) in HPMECs.
Conclusion: UFH protects the glycocalyx and endothelial barrier while inhibiting histone induced HPA expression, perinuclear distribution, and secretion, with the involvement of the ROCK pathway.