Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy
Background/Aims: The purpose of this study was to investigate the effect of administering particulate matter (PM2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process. Methods: Male Sprague D...
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Cell Physiol Biochem Press GmbH & Co KG
2018-04-01
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Online Access: | https://www.karger.com/Article/FullText/489192 |
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author | Fei Tong Hua Zhang |
author_facet | Fei Tong Hua Zhang |
author_sort | Fei Tong |
collection | DOAJ |
description | Background/Aims: The purpose of this study was to investigate the effect of administering particulate matter (PM2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process. Methods: Male Sprague Dawley (SD) rats were subjected to 45 min of ischemia, and the lungs were exposed to 2.0 mg of PM2.5 in 0.3 mL of normal saline 5 min before reperfusion. After 24 h of reperfusion, the blood and myocardium were collected, and the myocardial infarct sizes, activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cardiac troponin T (cTnT), P-selectin and D-dimer were measured via biochemical analysis. Additionally, the myeloperoxidase (MDA) content and superoxide dismutase (SOD) activity were measured in myocardial tissues via biochemical analysis, and the levels of reactive oxygen species (ROS), autophagosomes, microtubule-associated protein 1 light chain 3 (LC-I and II), macrophage inflammatory protein-2 (MIP-2) and farnesoid-X-receptor (FXR) were determined in myocardial tissues via biochemical analysis, immunohistochemical and biochemical techniques and western blot. In addition, the myocardial infarct sizes, LC-I and II expressions were determined in myocardial tissues through FXR-/- and WT mice. Results: Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in I/R group than that in Sham group, and Levels of IL-4 and SOD were lower in I/R group than that in Sham group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in I/R group than that in Sham group. Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in PM2.5 group than that in I/R group, and Levels of IL-4 and SOD were lower in PM2.5 group than that in I/R group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in PM2.5 group than that in I/R group. Conclusions: PM2.5 post-treatment exacerbated myocardial injury partly through upregulation of FXR to induce autophagy compared to MI/RI. |
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spelling | doaj.art-be48160e7bae40688e638a9d1e39a1a82022-12-21T18:34:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-04-014641493150710.1159/000489192489192Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced AutophagyFei TongHua ZhangBackground/Aims: The purpose of this study was to investigate the effect of administering particulate matter (PM2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process. Methods: Male Sprague Dawley (SD) rats were subjected to 45 min of ischemia, and the lungs were exposed to 2.0 mg of PM2.5 in 0.3 mL of normal saline 5 min before reperfusion. After 24 h of reperfusion, the blood and myocardium were collected, and the myocardial infarct sizes, activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cardiac troponin T (cTnT), P-selectin and D-dimer were measured via biochemical analysis. Additionally, the myeloperoxidase (MDA) content and superoxide dismutase (SOD) activity were measured in myocardial tissues via biochemical analysis, and the levels of reactive oxygen species (ROS), autophagosomes, microtubule-associated protein 1 light chain 3 (LC-I and II), macrophage inflammatory protein-2 (MIP-2) and farnesoid-X-receptor (FXR) were determined in myocardial tissues via biochemical analysis, immunohistochemical and biochemical techniques and western blot. In addition, the myocardial infarct sizes, LC-I and II expressions were determined in myocardial tissues through FXR-/- and WT mice. Results: Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in I/R group than that in Sham group, and Levels of IL-4 and SOD were lower in I/R group than that in Sham group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in I/R group than that in Sham group. Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in PM2.5 group than that in I/R group, and Levels of IL-4 and SOD were lower in PM2.5 group than that in I/R group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in PM2.5 group than that in I/R group. Conclusions: PM2.5 post-treatment exacerbated myocardial injury partly through upregulation of FXR to induce autophagy compared to MI/RI.https://www.karger.com/Article/FullText/489192Pm2.5Lung reperfusionMI/RIFXRAutophagy |
spellingShingle | Fei Tong Hua Zhang Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy Cellular Physiology and Biochemistry Pm2.5 Lung reperfusion MI/RI FXR Autophagy |
title | Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy |
title_full | Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy |
title_fullStr | Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy |
title_full_unstemmed | Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy |
title_short | Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy |
title_sort | pulmonary exposure to particulate matter pm2 5 affects the sensitivity to myocardial ischemia reperfusion injury through farnesoid x receptor induced autophagy |
topic | Pm2.5 Lung reperfusion MI/RI FXR Autophagy |
url | https://www.karger.com/Article/FullText/489192 |
work_keys_str_mv | AT feitong pulmonaryexposuretoparticulatematterpm25affectsthesensitivitytomyocardialischemiareperfusioninjurythroughfarnesoidxreceptorinducedautophagy AT huazhang pulmonaryexposuretoparticulatematterpm25affectsthesensitivitytomyocardialischemiareperfusioninjurythroughfarnesoidxreceptorinducedautophagy |