Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model

Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in ind...
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Autor*in:	Li-Fu Li [verfasserIn] Yung-Yang Liu [verfasserIn] Shih-Wei Lin [verfasserIn] Chih-Hao Chang [verfasserIn] Ning-Hung Chen [verfasserIn] Chen-Yiu Hung [verfasserIn] Chung-Shu Lee [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 21(2020), 9, p 3097
Übergeordnetes Werk:	volume:21 ; year:2020 ; number:9, p 3097

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms21093097

Katalog-ID:	DOAJ066372232

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520			\|a Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
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Indexfelder

author_variant	l f l lfl y y l yyl s w l swl c h c chc n h c nhc c y h cyh c s l csl
matchkey_str	article:14220067:2020----::omlclregteairdcsetltoidcdugnuyhoghpxanuilf
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allfields	10.3390/ijms21093097 doi (DE-627)DOAJ066372232 (DE-599)DOAJ78789355840a45019c83f36b68d61803 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Li-Fu Li verfasserin aut Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway. ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor Biology (General) Chemistry Yung-Yang Liu verfasserin aut Shih-Wei Lin verfasserin aut Chih-Hao Chang verfasserin aut Ning-Hung Chen verfasserin aut Chen-Yiu Hung verfasserin aut Chung-Shu Lee verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 9, p 3097 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:9, p 3097 https://doi.org/10.3390/ijms21093097 kostenfrei https://doaj.org/article/78789355840a45019c83f36b68d61803 kostenfrei https://www.mdpi.com/1422-0067/21/9/3097 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 9, p 3097
spelling	10.3390/ijms21093097 doi (DE-627)DOAJ066372232 (DE-599)DOAJ78789355840a45019c83f36b68d61803 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Li-Fu Li verfasserin aut Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway. ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor Biology (General) Chemistry Yung-Yang Liu verfasserin aut Shih-Wei Lin verfasserin aut Chih-Hao Chang verfasserin aut Ning-Hung Chen verfasserin aut Chen-Yiu Hung verfasserin aut Chung-Shu Lee verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 9, p 3097 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:9, p 3097 https://doi.org/10.3390/ijms21093097 kostenfrei https://doaj.org/article/78789355840a45019c83f36b68d61803 kostenfrei https://www.mdpi.com/1422-0067/21/9/3097 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 9, p 3097
allfields_unstemmed	10.3390/ijms21093097 doi (DE-627)DOAJ066372232 (DE-599)DOAJ78789355840a45019c83f36b68d61803 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Li-Fu Li verfasserin aut Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway. ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor Biology (General) Chemistry Yung-Yang Liu verfasserin aut Shih-Wei Lin verfasserin aut Chih-Hao Chang verfasserin aut Ning-Hung Chen verfasserin aut Chen-Yiu Hung verfasserin aut Chung-Shu Lee verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 9, p 3097 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:9, p 3097 https://doi.org/10.3390/ijms21093097 kostenfrei https://doaj.org/article/78789355840a45019c83f36b68d61803 kostenfrei https://www.mdpi.com/1422-0067/21/9/3097 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 9, p 3097
allfieldsGer	10.3390/ijms21093097 doi (DE-627)DOAJ066372232 (DE-599)DOAJ78789355840a45019c83f36b68d61803 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Li-Fu Li verfasserin aut Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway. ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor Biology (General) Chemistry Yung-Yang Liu verfasserin aut Shih-Wei Lin verfasserin aut Chih-Hao Chang verfasserin aut Ning-Hung Chen verfasserin aut Chen-Yiu Hung verfasserin aut Chung-Shu Lee verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 9, p 3097 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:9, p 3097 https://doi.org/10.3390/ijms21093097 kostenfrei https://doaj.org/article/78789355840a45019c83f36b68d61803 kostenfrei https://www.mdpi.com/1422-0067/21/9/3097 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 9, p 3097
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source	In International Journal of Molecular Sciences 21(2020), 9, p 3097 volume:21 year:2020 number:9, p 3097
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topic_title	QH301-705.5 QD1-999 Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model ventilator-induced lung injury endotoxemia low-molecular-weight heparin hypoxia-inducible factor
topic	misc QH301-705.5 misc QD1-999 misc ventilator-induced lung injury misc endotoxemia misc low-molecular-weight heparin misc hypoxia-inducible factor misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc ventilator-induced lung injury misc endotoxemia misc low-molecular-weight heparin misc hypoxia-inducible factor misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc ventilator-induced lung injury misc endotoxemia misc low-molecular-weight heparin misc hypoxia-inducible factor misc Biology (General) misc Chemistry
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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hierarchy_parent_title	International Journal of Molecular Sciences
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hierarchy_top_title	International Journal of Molecular Sciences
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title	Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model
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title_full	Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model
author_sort	Li-Fu Li
journal	International Journal of Molecular Sciences
journalStr	International Journal of Molecular Sciences
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author_browse	Li-Fu Li Yung-Yang Liu Shih-Wei Lin Chih-Hao Chang Ning-Hung Chen Chen-Yiu Hung Chung-Shu Lee
container_volume	21
class	QH301-705.5 QD1-999
format_se	Elektronische Aufsätze
author-letter	Li-Fu Li
doi_str_mv	10.3390/ijms21093097
author2-role	verfasserin
title_sort	low-molecular-weight heparin reduces ventilation-induced lung injury through hypoxia inducible factor-1α in a murine endotoxemia model
callnumber	QH301-705.5
title_auth	Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model
abstract	Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
abstractGer	Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
abstract_unstemmed	Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (<i<p</i< < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (<i<p</i< < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
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container_issue	9, p 3097
title_short	Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model
url	https://doi.org/10.3390/ijms21093097 https://doaj.org/article/78789355840a45019c83f36b68d61803 https://www.mdpi.com/1422-0067/21/9/3097 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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author2	Yung-Yang Liu Shih-Wei Lin Chih-Hao Chang Ning-Hung Chen Chen-Yiu Hung Chung-Shu Lee
author2Str	Yung-Yang Liu Shih-Wei Lin Chih-Hao Chang Ning-Hung Chen Chen-Yiu Hung Chung-Shu Lee
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up_date	2024-07-03T19:41:47.369Z
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