title: Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.
abstract: Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble-induced EMPs, which may be of great concern in DCS.
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Guoyang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Qing
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Diving and Hyperbaric Medicine, Faculty of Naval Medicine, the Second Military Medical University, Shanghai, China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley