H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

Background/Aims: The aim of present study was to test the hypothesis that preconditioning with sodium hydrosulfide (NaHS) could enhance the capacity of migration, adhesion and proliferation of endothelial progenitor cells (EPCs) in vitro, and also could improve the efficacy of EPCs transplantation for re-endothelialization in nude mice with carotid artery injury. The paper further addressed the underlying mechanisms. Methods: EPCs were isolated from peripheral blood mononuclear cells of healthy male volunteers and the markers of EPCs were analyzed by flow cytometry. Thereafter, different concentrations of NaHS (25, 50, 100, 200 and 500 uM) were used for preconditioning EPCs. In vitro and in vivo migration, adhesion and proliferation as well as nitric oxide (NO) production of EPCs were evaluated. Carotid artery injury model was produced in nude mice and thereafter, NaHS-preconditioned EPCs were transplanted in order to evaluate their capacity of re-endothelialization. Results: Cellular immuno-staining showed that isolated cells expressed the key markers of EPCs. In vitro, EPCs proliferation rates and NO production were gradually increased in a NaHS-concentration dependent manner, while these benefits were blocked at a concentration of 500 uM NaHS. Similarly, the migration and adhesion rates of EPCs were also increased the most prominently at a concentration of 200 µM NaHS. In vivo, compared to the control group, treatment with NaHS-preconditioned EPCs significantly enhanced the capacity of re-endothelialization of EPCs. Fluorescent microscope revealed that there were more EPCs homing to the injury vessels in the NaHS-preconditioned EPCs group than the non-preconditioned group. With the administration of AMPK or eNOS inhibitors respectively, the above benefits of NaHS-preconditioning were abrogated. Conclusion: These results suggested that NaHS-preconditioning enhanced the biological function and re-endothelialization of EPCs through the AMPK/eNOS signaling pathway.

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 97%

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Hydrogen Sulfide-Preconditioning of Human Endothelial Progenitor Cells Transplantation Improves Re-Endothelialization in Nude Mice with Carotid Artery Injury

Ke¹,

Zou²,

Hu³

et al. 2017

“…Histopathological analysis was performed as previously described [34]. The total area of the vascular walls was quantified with high-resolution images of individual vessels using a color-recognition algorithm in Image-Pro Plus 6.0 software.…”

Section: Methodsmentioning

confidence: 99%

PDGF-BB/KLF4/VEGF Signaling Axis in Pulmonary Artery Endothelial Cell Angiogenesis

Liang

Yu²,

Chen³

et al. 2017

Background: Accumulating evidence suggests that platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor(VEGF) play a role in the progression of pulmonary arterial hypertension (PAH).Since chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary arteries, which are histological hallmarks of PAH, we explored the role of the PDGF-BB/KLF4/VEGF signaling axis in the angiogenesis of pulmonary artery endothelial cells (PAECs). Methods: Adult male Wistar rats were used to study hypoxia-induced or monocrotaline (MCT)-induced right ventricular (RV) remodeling as well as systolic function and hemodynamics using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV vessels were performed. Results: The results revealed that both the PDGF receptor-tyrosine kinase inhibitor imatinib and the multi-targeted VEGF and PDGF receptor inhibit or sunitinib malate reversed hypoxia-induced increases in right ventricular systolic pressure (RVSP), right ventricular function and thickening of the medial walls. Mechanistically VEGF/VEGFR and PDGF/PDGFR formed a biological complex. We also showed that PDGF-BBincreasedKLF4 promoter activity transcriptionally activating VEGF expression, which regulates PAEC proliferation; migration; and the cell-cycle transition from G0/G1phase to S phase and G2/M-phase and eventually leads to PAEC angiogenesis Conclusion: Our study indicates that hypoxia-induced angiogenesis of PAECs is associated with increased levels of PDGF-BB/KLF4/VEGF, which contribute to pulmonary vascular remodeling. Overall, our study contributes to a better understanding of PAH pathogenesis.

“…ARDS is characterized by massive inflammatory cell infiltration, increased capillary permeability, severe alveolar damage and the formation of hyaline membranes [3][4][5][6]. The primary insults leading to ARDS include microbial infection, pollutants, toxic gasses, gastric acids, autoantibodies, fatty emboli, free fatty acids and transfusion [7,8].…”

Section: Introductionmentioning

confidence: 99%

ITRAQ-Based Proteomics Analysis of Acute Lung Injury Induced by Oleic Acid in Mice

Zhu

Zhang

et al. 2017

Background/Aims: This study was conducted to investigate the relationship between differentially expressed proteins (DEPs) and the pathogenesis of oleic acid (OA)-induced acute lung injury (ALI) in mice. Methods: Eight-week-old male C57BL/6 mice were injected with OA through the tail vein and sacrificed 6 hours after OA administration to identify protein expression levels in lung tissue using isobaric tags for relative and absolute quantification (iTRAQ) technology. Then, DEPs such as antithrombin III (AT III), 12-lipoxygenase (12-LO), dedicator of cytokinesis 2 (DOCK2), polycystin-2 and plasminogen were identified by western blotting. Subsequently, we focused on investigating the effect of AT III on endothelial integrity using siRNA interference technology. The levels of IL-6, IL-1β, TNF-α and TGF-β expression were detected using an enzyme-linked immunosorbent assay (ELISA). Alterations in the tight junction component ZO-1 and the phosphorylation of myosin light chain (pMLC) were determined by western blotting. The stress fiber F-actin were also detected by immunofluorescence staining. In addition, endothelial permeability was determined via a transwell permeability assay. Results: A total of 5152 proteins were found to be expressed in lung tissues from the OA-treated and saline-treated mice. Among these proteins, 849 were differentially expressed between the two groups, including 545 upregulated and 304 downregulated proteins. After AT III knockdown, the levels of inflammatory factors and endothelial permeability were elevated, the expression of ZO-1 was decreased, and the expression of F-actin and pMLC was increased. All these results illustrated that AT III knockdown exaggerated the disruption of endothelial integrity mediated by OA. Conclusion: These findings using iTRAQ technology demonstrate, for the first time, differences in the lung tissue expression levels of proteins between OA-treated mice and saline-treated mice. This study reveals that 12-LO, DOCK2 and especially AT III may be candidate biomarkers for OA-induced acute lung injury.