L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function
Abstract Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, rea...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202302123 |
| _version_ | 1827817720010244096 |
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| author | Zekun Wang Nana Yang Yajun Hou Yuqing Li Chenyang Yin Endong Yang Huanhuan Cao Gaofei Hu Jing Xue Jialei Yang Ziyu Liao Weiyun Wang Dongdong Sun Cundong Fan Lemin Zheng |
| author_facet | Zekun Wang Nana Yang Yajun Hou Yuqing Li Chenyang Yin Endong Yang Huanhuan Cao Gaofei Hu Jing Xue Jialei Yang Ziyu Liao Weiyun Wang Dongdong Sun Cundong Fan Lemin Zheng |
| author_sort | Zekun Wang |
| collection | DOAJ |
| description | Abstract Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L‐arginine‐loaded selenium‐coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)‐induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI. |
| first_indexed | 2024-03-12T00:37:40Z |
| format | Article |
| id | doaj.art-e527631db2af4e0183ec4b88a68ef4d3 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T00:37:40Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-e527631db2af4e0183ec4b88a68ef4d32023-09-15T09:28:59ZengWileyAdvanced Science2198-38442023-09-011026n/an/a10.1002/advs.202302123L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial FunctionZekun Wang0Nana Yang1Yajun Hou2Yuqing Li3Chenyang Yin4Endong Yang5Huanhuan Cao6Gaofei Hu7Jing Xue8Jialei Yang9Ziyu Liao10Weiyun Wang11Dongdong Sun12Cundong Fan13Lemin Zheng14School of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaSchool of Bioscience and Technology Weifang Key Laboratory of Animal Model Research on Cardiovascular and Cerebrovascular Diseases Weifang Medical University Weifang 261053 ChinaDepartment of Neurology Second Affiliated Hospital Shandong First Medical University & Shandong Academy of Medical Sciences Taian Shandong 271000 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaThe Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical Sciences State Key Laboratory of Vascular Homeostasis and Remodeling NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Health Science Center Peking University Beijing 100191 ChinaThe Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical Sciences State Key Laboratory of Vascular Homeostasis and Remodeling NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Health Science Center Peking University Beijing 100191 ChinaDepartment of Neurology China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaDepartment of Neurology China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaSchool of Life Sciences Anhui Agricultural University Hefei Anhui 230036 ChinaDepartment of Neurology Second Affiliated Hospital Shandong First Medical University & Shandong Academy of Medical Sciences Taian Shandong 271000 ChinaThe Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical Sciences State Key Laboratory of Vascular Homeostasis and Remodeling NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Health Science Center Peking University Beijing 100191 ChinaAbstract Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L‐arginine‐loaded selenium‐coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)‐induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.https://doi.org/10.1002/advs.202302123L‐argininemitochondrial functionmyocardial functionmyocardial ischaemia/reperfusion injurynitric oxidereactive oxygen species |
| spellingShingle | Zekun Wang Nana Yang Yajun Hou Yuqing Li Chenyang Yin Endong Yang Huanhuan Cao Gaofei Hu Jing Xue Jialei Yang Ziyu Liao Weiyun Wang Dongdong Sun Cundong Fan Lemin Zheng L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function Advanced Science L‐arginine mitochondrial function myocardial function myocardial ischaemia/reperfusion injury nitric oxide reactive oxygen species |
| title | L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function |
| title_full | L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function |
| title_fullStr | L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function |
| title_full_unstemmed | L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function |
| title_short | L‐Arginine‐Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function |
| title_sort | l arginine loaded gold nanocages ameliorate myocardial ischemia reperfusion injury by promoting nitric oxide production and maintaining mitochondrial function |
| topic | L‐arginine mitochondrial function myocardial function myocardial ischaemia/reperfusion injury nitric oxide reactive oxygen species |
| url | https://doi.org/10.1002/advs.202302123 |
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