DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation
Background Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, t...
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| Format: | Article |
| Language: | English |
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Korean Endocrine Society
2022-10-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://www.e-enm.org/upload/pdf/enm-2022-1462.pdf |
| _version_ | 1828158667571068928 |
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| author | Sudeep Kumar Jonghwa Jin Hyeon Young Park Mi-Jin Kim Jungwook Chin Sungwoo Lee Jina Kim Jung-Guk Kim Yeon-Kyung Choi Keun-Gyu Park |
| author_facet | Sudeep Kumar Jonghwa Jin Hyeon Young Park Mi-Jin Kim Jungwook Chin Sungwoo Lee Jina Kim Jung-Guk Kim Yeon-Kyung Choi Keun-Gyu Park |
| author_sort | Sudeep Kumar |
| collection | DOAJ |
| description | Background Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation. Methods VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice. Results DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice. Conclusion Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis. |
| first_indexed | 2024-04-11T23:48:33Z |
| format | Article |
| id | doaj.art-5b5612ebfc1b424b9c7851e123404bde |
| institution | Directory Open Access Journal |
| issn | 2093-596X 2093-5978 |
| language | English |
| last_indexed | 2024-04-11T23:48:33Z |
| publishDate | 2022-10-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj.art-5b5612ebfc1b424b9c7851e123404bde2022-12-22T03:56:34ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782022-10-0137580080910.3803/EnM.2022.14622332DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery LigationSudeep Kumar0Jonghwa Jin1Hyeon Young Park2Mi-Jin Kim3Jungwook Chin4Sungwoo Lee5Jina Kim6Jung-Guk Kim7Yeon-Kyung Choi8Keun-Gyu Park9 Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, Korea Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu, Korea New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu, Korea New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu, Korea Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, Korea Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, KoreaBackground Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation. Methods VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice. Results DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice. Conclusion Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.http://www.e-enm.org/upload/pdf/enm-2022-1462.pdfmuscle, smooth, vascularneointimaestrogen-related receptor gamma proteinoxidative phosphorylationmechanistic target of rapamycin complex 1 |
| spellingShingle | Sudeep Kumar Jonghwa Jin Hyeon Young Park Mi-Jin Kim Jungwook Chin Sungwoo Lee Jina Kim Jung-Guk Kim Yeon-Kyung Choi Keun-Gyu Park DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation Endocrinology and Metabolism muscle, smooth, vascular neointima estrogen-related receptor gamma protein oxidative phosphorylation mechanistic target of rapamycin complex 1 |
| title | DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation |
| title_full | DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation |
| title_fullStr | DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation |
| title_full_unstemmed | DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation |
| title_short | DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation |
| title_sort | dn200434 inhibits vascular smooth muscle cell proliferation and prevents neointima formation in mice after carotid artery ligation |
| topic | muscle, smooth, vascular neointima estrogen-related receptor gamma protein oxidative phosphorylation mechanistic target of rapamycin complex 1 |
| url | http://www.e-enm.org/upload/pdf/enm-2022-1462.pdf |
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