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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Main Authors: Fei Tong, Hua Zhang
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-04-01
Series:Cellular Physiology and Biochemistry
Subjects:
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