CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

Ming Horng Tsai; Chiang Wen Lee; Lee Fen Hsu; Shu Yu Li; Yao Chang Chiang; Ming Hsueh Lee; Chun Han Chen; Hwey Fang Liang; Jia Mei How; Pey Jium Chang; Ching Mei Wu; I-Ta Lee

doi:10.1016/j.redox.2017.02.019

CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

Ming Horng Tsai, Chiang Wen Lee, Lee Fen Hsu, Shu Yu Li, Yao Chang Chiang, Ming Hsueh Lee, Chun Han Chen, Hwey Fang Liang, Jia Mei How, Pey Jium Chang, Ching Mei Wu, I-Ta Lee

研究成果: 雜誌貢獻 › 文章 › 同行評審

28 引文斯高帕斯（Scopus）

摘要

Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47 phox , Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47 phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed.

原文	英語
頁（從 - 到）	377-388
頁數	12
期刊	Redox Biology
卷	12
DOIs	https://doi.org/10.1016/j.redox.2017.02.019
出版狀態	已發佈 - 8月 1 2017
對外發佈	是

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生物化學
有機化學

UN SDG

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10.1016/j.redox.2017.02.019

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Tsai, M. H., Lee, C. W., Hsu, L. F., Li, S. Y., Chiang, Y. C., Lee, M. H., Chen, C. H., Liang, H. F., How, J. M., Chang, P. J., Wu, C. M., & Lee, I-T. (2017). CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression. Redox Biology, 12, 377-388. https://doi.org/10.1016/j.redox.2017.02.019

Tsai, MH, Lee, CW, Hsu, LF, Li, SY, Chiang, YC, Lee, MH, Chen, CH, Liang, HF, How, JM, Chang, PJ, Wu, CM & Lee, I-T 2017, 'CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression', Redox Biology, 卷 12, 頁 377-388. https://doi.org/10.1016/j.redox.2017.02.019

@article{1721b4001756472dbd6c38d4f08c4656,

title = "CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression",

abstract = "Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47 phox , Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47 phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed.",

keywords = "Angiotensin II, Carbon monoxide, Human aortic smooth muscle cell, Inflammation, Matrix metallopeptidase-9",

author = "Tsai, {Ming Horng} and Lee, {Chiang Wen} and Hsu, {Lee Fen} and Li, {Shu Yu} and Chiang, {Yao Chang} and Lee, {Ming Hsueh} and Chen, {Chun Han} and Liang, {Hwey Fang} and How, {Jia Mei} and Chang, {Pey Jium} and Wu, {Ching Mei} and I-Ta Lee",

note = "Funding Information: We thank Ms. Sin-Yu Li for their technical assistance. This work was supported by the Chang Gung Medical Research Foundation, grant number CMRPGMF0031, CMRPGMC0011, CMRPGMC0012, and CMRPGME0021; the Ministry of Science and Technology, Taiwan, grant number MOST 104-2320-B-039-043; the China Medical University, grant number CMU105-S-46, CMU104-N-05, and CMU105-N-22. Publisher Copyright: {\textcopyright} 2017",

year = "2017",

month = aug,

day = "1",

doi = "10.1016/j.redox.2017.02.019",

language = "English",

volume = "12",

pages = "377--388",

journal = "Redox Biology",

issn = "2213-2317",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

AU - Tsai, Ming Horng

AU - Lee, Chiang Wen

AU - Hsu, Lee Fen

AU - Li, Shu Yu

AU - Chiang, Yao Chang

AU - Lee, Ming Hsueh

AU - Chen, Chun Han

AU - Liang, Hwey Fang

AU - How, Jia Mei

AU - Chang, Pey Jium

AU - Wu, Ching Mei

AU - Lee, I-Ta

N1 - Funding Information: We thank Ms. Sin-Yu Li for their technical assistance. This work was supported by the Chang Gung Medical Research Foundation, grant number CMRPGMF0031, CMRPGMC0011, CMRPGMC0012, and CMRPGME0021; the Ministry of Science and Technology, Taiwan, grant number MOST 104-2320-B-039-043; the China Medical University, grant number CMU105-S-46, CMU104-N-05, and CMU105-N-22. Publisher Copyright: © 2017

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47 phox , Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47 phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed.

AB - Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47 phox , Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47 phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed.

KW - Angiotensin II

KW - Carbon monoxide

KW - Human aortic smooth muscle cell

KW - Inflammation

KW - Matrix metallopeptidase-9

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UR - http://www.scopus.com/inward/citedby.url?scp=85015106903&partnerID=8YFLogxK

U2 - 10.1016/j.redox.2017.02.019

DO - 10.1016/j.redox.2017.02.019

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AN - SCOPUS:85015106903

SN - 2213-2317

VL - 12

SP - 377

EP - 388

JO - Redox Biology

JF - Redox Biology

ER -

CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

摘要

ASJC Scopus subject areas

UN SDG

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