Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque
Background and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.642751/full |
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| author | Xueyu Wang Xueyu Wang Yahong Fu Yahong Fu Zulong Xie Muhua Cao Muhua Cao Wenbo Qu Wenbo Qu Xiangwen Xi Xiangwen Xi Shan Zhong Shan Zhong Minghui Piao Minghui Piao Xiang Peng Xiang Peng Ying Jia Ying Jia Lingbo Meng Jinwei Tian |
| author_facet | Xueyu Wang Xueyu Wang Yahong Fu Yahong Fu Zulong Xie Muhua Cao Muhua Cao Wenbo Qu Wenbo Qu Xiangwen Xi Xiangwen Xi Shan Zhong Shan Zhong Minghui Piao Minghui Piao Xiang Peng Xiang Peng Ying Jia Ying Jia Lingbo Meng Jinwei Tian |
| author_sort | Xueyu Wang |
| collection | DOAJ |
| description | Background and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice were crossbred with LDLR−/− mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.Results: Compared to control mice, Fbn1C1039G+/−LDLR−/− mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/− mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.Conclusions: Plaques in Fbn1C1039G+/−LDLR−/− mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/− mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques. |
| first_indexed | 2024-12-16T16:03:22Z |
| format | Article |
| id | doaj.art-904f2d96d8f841e9a4411515bc6deb33 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-16T16:03:22Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-904f2d96d8f841e9a4411515bc6deb332022-12-21T22:25:25ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-03-01810.3389/fcvm.2021.642751642751Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable PlaqueXueyu Wang0Xueyu Wang1Yahong Fu2Yahong Fu3Zulong Xie4Muhua Cao5Muhua Cao6Wenbo Qu7Wenbo Qu8Xiangwen Xi9Xiangwen Xi10Shan Zhong11Shan Zhong12Minghui Piao13Minghui Piao14Xiang Peng15Xiang Peng16Ying Jia17Ying Jia18Lingbo Meng19Jinwei Tian20Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackground and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice were crossbred with LDLR−/− mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.Results: Compared to control mice, Fbn1C1039G+/−LDLR−/− mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/− mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.Conclusions: Plaques in Fbn1C1039G+/−LDLR−/− mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/− mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.https://www.frontiersin.org/articles/10.3389/fcvm.2021.642751/fullatherosclerosisvulnerable plaqueanimal modelplaque ruptureFbn1C1039G +/–LDLR–/– mice |
| spellingShingle | Xueyu Wang Xueyu Wang Yahong Fu Yahong Fu Zulong Xie Muhua Cao Muhua Cao Wenbo Qu Wenbo Qu Xiangwen Xi Xiangwen Xi Shan Zhong Shan Zhong Minghui Piao Minghui Piao Xiang Peng Xiang Peng Ying Jia Ying Jia Lingbo Meng Jinwei Tian Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque Frontiers in Cardiovascular Medicine atherosclerosis vulnerable plaque animal model plaque rupture Fbn1C1039G +/–LDLR–/– mice |
| title | Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque |
| title_full | Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque |
| title_fullStr | Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque |
| title_full_unstemmed | Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque |
| title_short | Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque |
| title_sort | establishment of a novel mouse model for atherosclerotic vulnerable plaque |
| topic | atherosclerosis vulnerable plaque animal model plaque rupture Fbn1C1039G +/–LDLR–/– mice |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.642751/full |
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