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
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, exe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717300666 |
| id |
doaj-857731228a4c4d8898802c8a62050a55 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 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 |
| author_facet |
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 |
| author_sort |
Ming-Horng Tsai |
| 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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Elsevier |
| series |
Redox Biology |
| issn |
2213-2317 |
| publishDate |
2017-08-01 |
| description |
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 p47phox, 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 p47phox 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 |
| url |
http://www.sciencedirect.com/science/article/pii/S2213231717300666 |
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doaj-857731228a4c4d8898802c8a62050a552020-11-25T01:32:02ZengElsevierRedox Biology2213-23172017-08-0112377388CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expressionMing-Horng Tsai0Chiang-Wen Lee1Lee-Fen Hsu2Shu-Yu Li3Yao-Chang Chiang4Ming-Hsueh Lee5Chun-Han Chen6Hwey-Fang Liang7Jia-Mei How8Pey-Jium Chang9Ching-Mei Wu10I-Ta Lee11Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, TaiwanDepartment of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Correspondence to: Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University Of Science and Technology, Chia-Yi, Taiwan.Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, TaiwanDepartment of Pharmacy, College of Pharmacy & Health Care, Tajen University, TaiwanCenter for Drug Abuse and Addiction, China Medical University Hospital, China Medical University, Taichung, TaiwanDivision of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi 61363, TaiwanDivision of General Surgery, Department of Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, TaiwanDepartment of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, TaiwanSchool of Medicine, College of Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, TaiwanDepartment of Sports Medicine, College of Health Care, China Medical University, Taichung, TaiwanSchool of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan; Correspondence to: School of Medicine, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan, R.O.C.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 p47phox, 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 p47phox 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-9http://www.sciencedirect.com/science/article/pii/S2213231717300666 |