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Published on: May 21, 2018
Endothelial Microvesicles Induce Pulmonary Vascular Leakage and Lung Injury During Sepsis
Danyang Zheng1, Jie Zhang1, Zisen Zhang1
1State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
Abstract:
Sepsis is a prevalent severe syndrome in clinic. Vascular leakage and lung injury are important pathophysiological processes during sepsis, but the mechanism remains obscure. Microvesicles (MVs) play an essential role in many diseases, while whether MVs participate in vascular leakage and lung injury during sepsis is unknown. Using cecal ligation and puncture induced sepsis rats and lipopolysaccharide stimulated vascular endothelial cells (VECs), the role and the underlying mechanism of endothelial microvesicles (EMVs) in pulmonary vascular leakage and lung injury were observed. The role of MVs from sepsis patients was verified. The results showed that the concentration of MVs in blood was significantly increased after sepsis. MVs from sepsis rats and patients induced apparent pulmonary vascular leakage and lung injury, among which EMVs played the dominant role, in which miR-23b was the key inducing factor in vascular leakage. Furthermore, downregulation and upregulation of miR-23b in EMVs showed that miR-23b mainly targeted on ZO-1 to induce vascular leakage. MVs from sepsis patients induced pulmonary vascular leakage and lung injury in normal rats. Application of classic antidepressants amitriptyline reduced the secretion of EMVs, and alleviated vascular leakage and lung injury. The study suggests that EMVs play an important role in pulmonary vascular leakage and lung injury during sepsis by transferring functional miR-23b. Antagonizing the secretion of EMVs and the miR-23b might be a potential target for the treatment of severe sepsis.
Insights
Microvesicles from sepsis patients and rats cause lung injury and vascular leakage. Endothelial microvesicles (EMVs) are key, transferring miR-23b to damage ZO-1, suggesting new sepsis treatment targets.
Area of Science:
- Cell Biology
- Pathophysiology
- Molecular Biology
Background:
- Sepsis is a severe clinical syndrome characterized by vascular leakage and lung injury.
- The precise mechanisms driving sepsis-induced vascular leakage and lung injury remain unclear.
- The role of microvesicles (MVs), particularly endothelial microvesicles (EMVs), in sepsis pathophysiology is largely unknown.
Purpose of the Study:
- To investigate the role and underlying mechanisms of EMVs in pulmonary vascular leakage and lung injury during sepsis.
- To determine if MVs from sepsis patients contribute to these pathological processes.
- To explore potential therapeutic targets for sepsis-induced complications.
Main Methods:
- Established sepsis models in rats using cecal ligation and puncture (CLP).
- Utilized lipopolysaccharide (LPS)-stimulated vascular endothelial cells (VECs) in vitro.
- Analyzed MVs in sepsis patients and their effects on normal rats; manipulated miR-23b levels in EMVs and assessed ZO-1 expression.
Main Results:
- Sepsis significantly increased circulating MV concentration.
- MVs from sepsis rats and patients induced pulmonary vascular leakage and lung injury, with EMVs playing a dominant role.
- miR-23b within EMVs was identified as a key factor inducing vascular leakage by targeting ZO-1; amitriptyline reduced EMV secretion and mitigated injury.
Conclusions:
- EMVs are critical mediators of pulmonary vascular leakage and lung injury in sepsis via transfer of functional miR-23b.
- Targeting EMV secretion and miR-23b represents a potential therapeutic strategy for severe sepsis.
- Findings highlight a novel mechanism in sepsis pathophysiology and suggest new avenues for treatment.
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