Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1

BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Xueting Qiu [verfasserIn] Jipeng Zhou [verfasserIn] Yanying Xu [verfasserIn] Longsheng Liao [verfasserIn] Huijun Yang [verfasserIn] Yuan Xiang [verfasserIn] Zhengshi Zhou [verfasserIn] Quan Sun [verfasserIn] Minghong Chen [verfasserIn] Jiaxiong Zhang [verfasserIn] Wanzhou Wu [verfasserIn] Lingping Zhu [verfasserIn] Baiyang You [verfasserIn] Lingfang He [verfasserIn] Ying Luo [verfasserIn] Zhenyu Li [verfasserIn] Chuanchang Li [verfasserIn] Yongping Bai [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	exercise miR-125a-5p circulating exosome revascularization

Übergeordnetes Werk:	In: Frontiers in Cardiovascular Medicine - Frontiers Media S.A., 2015, 9(2022)
Übergeordnetes Werk:	volume:9 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcvm.2022.881526

Katalog-ID:	DOAJ024584703

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245	1	0	\|a Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
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520			\|a BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.
650		4	\|a exercise
650		4	\|a miR-125a-5p
650		4	\|a circulating
650		4	\|a exosome
650		4	\|a revascularization
653		0	\|a Diseases of the circulatory (Cardiovascular) system
700	0		\|a Jipeng Zhou \|e verfasserin \|4 aut
700	0		\|a Jipeng Zhou \|e verfasserin \|4 aut
700	0		\|a Yanying Xu \|e verfasserin \|4 aut
700	0		\|a Longsheng Liao \|e verfasserin \|4 aut
700	0		\|a Huijun Yang \|e verfasserin \|4 aut
700	0		\|a Yuan Xiang \|e verfasserin \|4 aut
700	0		\|a Zhengshi Zhou \|e verfasserin \|4 aut
700	0		\|a Quan Sun \|e verfasserin \|4 aut
700	0		\|a Minghong Chen \|e verfasserin \|4 aut
700	0		\|a Jiaxiong Zhang \|e verfasserin \|4 aut
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700	0		\|a Lingping Zhu \|e verfasserin \|4 aut
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700	0		\|a Zhenyu Li \|e verfasserin \|4 aut
700	0		\|a Chuanchang Li \|e verfasserin \|4 aut
700	0		\|a Chuanchang Li \|e verfasserin \|4 aut
700	0		\|a Yongping Bai \|e verfasserin \|4 aut
700	0		\|a Yongping Bai \|e verfasserin \|4 aut
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allfields	10.3389/fcvm.2022.881526 doi (DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036 DE-627 ger DE-627 rakwb eng RC666-701 Xueting Qiu verfasserin aut Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system Jipeng Zhou verfasserin aut Jipeng Zhou verfasserin aut Yanying Xu verfasserin aut Longsheng Liao verfasserin aut Huijun Yang verfasserin aut Yuan Xiang verfasserin aut Zhengshi Zhou verfasserin aut Quan Sun verfasserin aut Minghong Chen verfasserin aut Jiaxiong Zhang verfasserin aut Wanzhou Wu verfasserin aut Lingping Zhu verfasserin aut Baiyang You verfasserin aut Lingfang He verfasserin aut Ying Luo verfasserin aut Zhenyu Li verfasserin aut Chuanchang Li verfasserin aut Chuanchang Li verfasserin aut Yongping Bai verfasserin aut Yongping Bai verfasserin aut In Frontiers in Cardiovascular Medicine Frontiers Media S.A., 2015 9(2022) (DE-627)793951607 (DE-600)2781496-8 2297055X nnns volume:9 year:2022 https://doi.org/10.3389/fcvm.2022.881526 kostenfrei https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 kostenfrei https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full kostenfrei https://doaj.org/toc/2297-055X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 9 2022
spelling	10.3389/fcvm.2022.881526 doi (DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036 DE-627 ger DE-627 rakwb eng RC666-701 Xueting Qiu verfasserin aut Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system Jipeng Zhou verfasserin aut Jipeng Zhou verfasserin aut Yanying Xu verfasserin aut Longsheng Liao verfasserin aut Huijun Yang verfasserin aut Yuan Xiang verfasserin aut Zhengshi Zhou verfasserin aut Quan Sun verfasserin aut Minghong Chen verfasserin aut Jiaxiong Zhang verfasserin aut Wanzhou Wu verfasserin aut Lingping Zhu verfasserin aut Baiyang You verfasserin aut Lingfang He verfasserin aut Ying Luo verfasserin aut Zhenyu Li verfasserin aut Chuanchang Li verfasserin aut Chuanchang Li verfasserin aut Yongping Bai verfasserin aut Yongping Bai verfasserin aut In Frontiers in Cardiovascular Medicine Frontiers Media S.A., 2015 9(2022) (DE-627)793951607 (DE-600)2781496-8 2297055X nnns volume:9 year:2022 https://doi.org/10.3389/fcvm.2022.881526 kostenfrei https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 kostenfrei https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full kostenfrei https://doaj.org/toc/2297-055X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 9 2022
allfields_unstemmed	10.3389/fcvm.2022.881526 doi (DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036 DE-627 ger DE-627 rakwb eng RC666-701 Xueting Qiu verfasserin aut Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system Jipeng Zhou verfasserin aut Jipeng Zhou verfasserin aut Yanying Xu verfasserin aut Longsheng Liao verfasserin aut Huijun Yang verfasserin aut Yuan Xiang verfasserin aut Zhengshi Zhou verfasserin aut Quan Sun verfasserin aut Minghong Chen verfasserin aut Jiaxiong Zhang verfasserin aut Wanzhou Wu verfasserin aut Lingping Zhu verfasserin aut Baiyang You verfasserin aut Lingfang He verfasserin aut Ying Luo verfasserin aut Zhenyu Li verfasserin aut Chuanchang Li verfasserin aut Chuanchang Li verfasserin aut Yongping Bai verfasserin aut Yongping Bai verfasserin aut In Frontiers in Cardiovascular Medicine Frontiers Media S.A., 2015 9(2022) (DE-627)793951607 (DE-600)2781496-8 2297055X nnns volume:9 year:2022 https://doi.org/10.3389/fcvm.2022.881526 kostenfrei https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 kostenfrei https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full kostenfrei https://doaj.org/toc/2297-055X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 9 2022
allfieldsGer	10.3389/fcvm.2022.881526 doi (DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036 DE-627 ger DE-627 rakwb eng RC666-701 Xueting Qiu verfasserin aut Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system Jipeng Zhou verfasserin aut Jipeng Zhou verfasserin aut Yanying Xu verfasserin aut Longsheng Liao verfasserin aut Huijun Yang verfasserin aut Yuan Xiang verfasserin aut Zhengshi Zhou verfasserin aut Quan Sun verfasserin aut Minghong Chen verfasserin aut Jiaxiong Zhang verfasserin aut Wanzhou Wu verfasserin aut Lingping Zhu verfasserin aut Baiyang You verfasserin aut Lingfang He verfasserin aut Ying Luo verfasserin aut Zhenyu Li verfasserin aut Chuanchang Li verfasserin aut Chuanchang Li verfasserin aut Yongping Bai verfasserin aut Yongping Bai verfasserin aut In Frontiers in Cardiovascular Medicine Frontiers Media S.A., 2015 9(2022) (DE-627)793951607 (DE-600)2781496-8 2297055X nnns volume:9 year:2022 https://doi.org/10.3389/fcvm.2022.881526 kostenfrei https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 kostenfrei https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full kostenfrei https://doaj.org/toc/2297-055X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 9 2022
allfieldsSound	10.3389/fcvm.2022.881526 doi (DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036 DE-627 ger DE-627 rakwb eng RC666-701 Xueting Qiu verfasserin aut Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease. exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system Jipeng Zhou verfasserin aut Jipeng Zhou verfasserin aut Yanying Xu verfasserin aut Longsheng Liao verfasserin aut Huijun Yang verfasserin aut Yuan Xiang verfasserin aut Zhengshi Zhou verfasserin aut Quan Sun verfasserin aut Minghong Chen verfasserin aut Jiaxiong Zhang verfasserin aut Wanzhou Wu verfasserin aut Lingping Zhu verfasserin aut Baiyang You verfasserin aut Lingfang He verfasserin aut Ying Luo verfasserin aut Zhenyu Li verfasserin aut Chuanchang Li verfasserin aut Chuanchang Li verfasserin aut Yongping Bai verfasserin aut Yongping Bai verfasserin aut In Frontiers in Cardiovascular Medicine Frontiers Media S.A., 2015 9(2022) (DE-627)793951607 (DE-600)2781496-8 2297055X nnns volume:9 year:2022 https://doi.org/10.3389/fcvm.2022.881526 kostenfrei https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 kostenfrei https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full kostenfrei https://doaj.org/toc/2297-055X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 9 2022
language	English
source	In Frontiers in Cardiovascular Medicine 9(2022) volume:9 year:2022
sourceStr	In Frontiers in Cardiovascular Medicine 9(2022) volume:9 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	exercise miR-125a-5p circulating exosome revascularization Diseases of the circulatory (Cardiovascular) system
isfreeaccess_bool	true
container_title	Frontiers in Cardiovascular Medicine
authorswithroles_txt_mv	Xueting Qiu @@aut@@ Jipeng Zhou @@aut@@ Yanying Xu @@aut@@ Longsheng Liao @@aut@@ Huijun Yang @@aut@@ Yuan Xiang @@aut@@ Zhengshi Zhou @@aut@@ Quan Sun @@aut@@ Minghong Chen @@aut@@ Jiaxiong Zhang @@aut@@ Wanzhou Wu @@aut@@ Lingping Zhu @@aut@@ Baiyang You @@aut@@ Lingfang He @@aut@@ Ying Luo @@aut@@ Zhenyu Li @@aut@@ Chuanchang Li @@aut@@ Yongping Bai @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	793951607
id	DOAJ024584703
language_de	englisch
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Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">exercise</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">miR-125a-5p</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">circulating</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">exosome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">revascularization</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the circulatory (Cardiovascular) system</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jipeng Zhou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jipeng Zhou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yanying Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Longsheng Liao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huijun Yang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yuan Xiang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhengshi Zhou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield 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callnumber-first	R - Medicine
author	Xueting Qiu
spellingShingle	Xueting Qiu misc RC666-701 misc exercise misc miR-125a-5p misc circulating misc exosome misc revascularization misc Diseases of the circulatory (Cardiovascular) system Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
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topic_title	RC666-701 Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1 exercise miR-125a-5p circulating exosome revascularization
topic	misc RC666-701 misc exercise misc miR-125a-5p misc circulating misc exosome misc revascularization misc Diseases of the circulatory (Cardiovascular) system
topic_unstemmed	misc RC666-701 misc exercise misc miR-125a-5p misc circulating misc exosome misc revascularization misc Diseases of the circulatory (Cardiovascular) system
topic_browse	misc RC666-701 misc exercise misc miR-125a-5p misc circulating misc exosome misc revascularization misc Diseases of the circulatory (Cardiovascular) system
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title	Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
ctrlnum	(DE-627)DOAJ024584703 (DE-599)DOAJ6953187372704d9fabf4b2e22b2b5036
title_full	Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
author_sort	Xueting Qiu
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author_browse	Xueting Qiu Jipeng Zhou Yanying Xu Longsheng Liao Huijun Yang Yuan Xiang Zhengshi Zhou Quan Sun Minghong Chen Jiaxiong Zhang Wanzhou Wu Lingping Zhu Baiyang You Lingfang He Ying Luo Zhenyu Li Chuanchang Li Yongping Bai
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title_sort	prophylactic exercise-derived circulating exosomal mir-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
callnumber	RC666-701
title_auth	Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
abstract	BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.
abstractGer	BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.
abstract_unstemmed	BackgroundProphylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.Methods and ResultsWe first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.ConclusionsEndogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.
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title_short	Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
url	https://doi.org/10.3389/fcvm.2022.881526 https://doaj.org/article/6953187372704d9fabf4b2e22b2b5036 https://www.frontiersin.org/articles/10.3389/fcvm.2022.881526/full https://doaj.org/toc/2297-055X
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author2	Jipeng Zhou Yanying Xu Longsheng Liao Huijun Yang Yuan Xiang Zhengshi Zhou Quan Sun Minghong Chen Jiaxiong Zhang Wanzhou Wu Lingping Zhu Baiyang You Lingfang He Ying Luo Zhenyu Li Chuanchang Li Yongping Bai
author2Str	Jipeng Zhou Yanying Xu Longsheng Liao Huijun Yang Yuan Xiang Zhengshi Zhou Quan Sun Minghong Chen Jiaxiong Zhang Wanzhou Wu Lingping Zhu Baiyang You Lingfang He Ying Luo Zhenyu Li Chuanchang Li Yongping Bai
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up_date	2024-07-03T23:35:11.278Z
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Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1

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