Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models
Abstract We investigated whether miR143#12, a synthesized chemically modified miR-143-3p derivative, exerts therapeutic effects on acute myocardial infarction (AMI). Sprague–Dawley rats and Japanese white rabbits underwent 30 min of coronary occlusion followed by 2 weeks of reperfusion. The rat AMI...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-76429-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544713566420992 |
|---|---|
| author | Shingo Minatoguchi Nobuhiko Sugito Kazuki Heishima Yuko Ito Remi Nakashima Hiroyuki Okura Yukihiro Akao Shinya Minatoguchi |
| author_facet | Shingo Minatoguchi Nobuhiko Sugito Kazuki Heishima Yuko Ito Remi Nakashima Hiroyuki Okura Yukihiro Akao Shinya Minatoguchi |
| author_sort | Shingo Minatoguchi |
| collection | DOAJ |
| description | Abstract We investigated whether miR143#12, a synthesized chemically modified miR-143-3p derivative, exerts therapeutic effects on acute myocardial infarction (AMI). Sprague–Dawley rats and Japanese white rabbits underwent 30 min of coronary occlusion followed by 2 weeks of reperfusion. The rat AMI model was intravenously administered with control miRNA (9 μg/kg), 3 μg/kg or 9 μg/kg of miR143#12 1 h after reperfusion, while the rabbit AMI model was intravenously administered with control miRNA (9 μg/kg) or 9 μg/kg of miR143#12. In the rat and rabbit AMI models, 9 μg/kg of miR143#12 significantly reduced infarct sizes and significantly improved cardiac function including LVEF and LVFS at 2 weeks. The tissue miR143 levels in infarct areas significantly decreased after AMI in both models. Electron microscopic study and immunohistochemistry suggested that miR143#12 suppressed autophagic cell death caused by AMI and induced neoangiogenesis in the infarct border. In cultured rat H9c2 cells, miR143#12 significantly inhibited H2O2-induced autophagic cell death by decreasing ROS levels and increased viable cell numbers more than the control by silencing COX-1, -2, and ATG7. Replacement treatment with miR143#12 in the infarct areas, where the expression levels of miR143 were significantly decreased, has a beneficial effect on AMI by silencing COX-1 and -2. |
| format | Article |
| id | doaj-art-03c4ce2f004e40d68d375eaa099e5fef |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-03c4ce2f004e40d68d375eaa099e5fef2025-01-12T12:20:08ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-76429-3Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal modelsShingo Minatoguchi0Nobuhiko Sugito1Kazuki Heishima2Yuko Ito3Remi Nakashima4Hiroyuki Okura5Yukihiro Akao6Shinya Minatoguchi7Department of Cardiology, Gifu University Graduate School of MedicineUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu UniversityUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu UniversityDepartment of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical UniversityUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu UniversityDepartment of Cardiology, Gifu University Graduate School of MedicineUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu UniversityDepartment of Circulatory and Respiratory Advanced Medicine, Gifu University Graduate School of MedicineAbstract We investigated whether miR143#12, a synthesized chemically modified miR-143-3p derivative, exerts therapeutic effects on acute myocardial infarction (AMI). Sprague–Dawley rats and Japanese white rabbits underwent 30 min of coronary occlusion followed by 2 weeks of reperfusion. The rat AMI model was intravenously administered with control miRNA (9 μg/kg), 3 μg/kg or 9 μg/kg of miR143#12 1 h after reperfusion, while the rabbit AMI model was intravenously administered with control miRNA (9 μg/kg) or 9 μg/kg of miR143#12. In the rat and rabbit AMI models, 9 μg/kg of miR143#12 significantly reduced infarct sizes and significantly improved cardiac function including LVEF and LVFS at 2 weeks. The tissue miR143 levels in infarct areas significantly decreased after AMI in both models. Electron microscopic study and immunohistochemistry suggested that miR143#12 suppressed autophagic cell death caused by AMI and induced neoangiogenesis in the infarct border. In cultured rat H9c2 cells, miR143#12 significantly inhibited H2O2-induced autophagic cell death by decreasing ROS levels and increased viable cell numbers more than the control by silencing COX-1, -2, and ATG7. Replacement treatment with miR143#12 in the infarct areas, where the expression levels of miR143 were significantly decreased, has a beneficial effect on AMI by silencing COX-1 and -2.https://doi.org/10.1038/s41598-024-76429-3Chemically modified miR143Myocardial infarctionInfarct sizeCardiac functionAutophagic cell deathAngiogenesis |
| spellingShingle | Shingo Minatoguchi Nobuhiko Sugito Kazuki Heishima Yuko Ito Remi Nakashima Hiroyuki Okura Yukihiro Akao Shinya Minatoguchi Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models Scientific Reports Chemically modified miR143 Myocardial infarction Infarct size Cardiac function Autophagic cell death Angiogenesis |
| title | Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models |
| title_full | Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models |
| title_fullStr | Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models |
| title_full_unstemmed | Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models |
| title_short | Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models |
| title_sort | restoration effect of chemically modified microrna 143 3p on acute myocardial infarction in animal models |
| topic | Chemically modified miR143 Myocardial infarction Infarct size Cardiac function Autophagic cell death Angiogenesis |
| url | https://doi.org/10.1038/s41598-024-76429-3 |
| work_keys_str_mv | AT shingominatoguchi restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT nobuhikosugito restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT kazukiheishima restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT yukoito restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT reminakashima restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT hiroyukiokura restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT yukihiroakao restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels AT shinyaminatoguchi restorationeffectofchemicallymodifiedmicrorna1433ponacutemyocardialinfarctioninanimalmodels |