Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models
BackgroundIntracranial atherosclerosis (ICAS) is one of the most common causes of ischemic stroke, but there are few animal models that can recapitulate its pathological features. In this study, we examined ICAS pathological features and anatomic distributions using three types of hyperlipidemic rab...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.834207/full |
| _version_ | 1818243290376437760 |
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| author | Xiangming Tang Manabu Niimi Huanjin Zhou Lu Chen Yajie Chen Haizhao Yan Masashi Shiomi Jianglin Fan Jianglin Fan |
| author_facet | Xiangming Tang Manabu Niimi Huanjin Zhou Lu Chen Yajie Chen Haizhao Yan Masashi Shiomi Jianglin Fan Jianglin Fan |
| author_sort | Xiangming Tang |
| collection | DOAJ |
| description | BackgroundIntracranial atherosclerosis (ICAS) is one of the most common causes of ischemic stroke, but there are few animal models that can recapitulate its pathological features. In this study, we examined ICAS pathological features and anatomic distributions using three types of hyperlipidemic rabbit models. We also investigated the effect of different lipoprotein profiles and hypertension on ICAS.Materials and MethodsWe examined Watanabe heritable hyperlipidemic (WHHL) rabbits, apoE knockout (KO) rabbits and wild-type rabbits (WT) fed a cholesterol diet, in addition to WT rabbits fed a standard diet as a control. The whole brain was dissected and embedded in paraffin. Serial sections were stained with either hematoxylin/eosin or elastica van Gieson, or immunohistochemically stained with monoclonal antibodies against macrophages and smooth muscle cells. We investigated (1) the presence of cerebral atherosclerosis; (2) the lesion locations in the cerebral arteries; (3) the degree of lumen stenosis; (4) pathological features and cellular components of the lesions in these rabbits; and (5) whether hypertension affects ICAS.ResultsICAS was detected in apoE and WHHL rabbits, but not in WT rabbits. Compared with apoE KO rabbits, WHHL rabbits had greater ICAS. The lesions of cerebral atherosclerosis were mainly distributed at the bifurcations of the posterior cerebral artery, basilar artery and vertebral artery, and they were basically characterized by smooth muscle cells and extracellular matrix with few macrophages. The extent of the ICAS in WHHL rabbits was significantly increased by hypertension.ConclusionsICAS was detected in WHHL and apoE KO rabbits, and occurred in specific locations in the cerebral arteries. Hypertension promotes the development of ICAS in the setting of hypercholesterolemia. |
| first_indexed | 2024-12-12T13:58:46Z |
| format | Article |
| id | doaj.art-b2b74d157bed4b2994cf36aab71c4160 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-12T13:58:46Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-b2b74d157bed4b2994cf36aab71c41602022-12-22T00:22:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-05-011310.3389/fendo.2022.834207834207Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit ModelsXiangming Tang0Manabu Niimi1Huanjin Zhou2Lu Chen3Yajie Chen4Haizhao Yan5Masashi Shiomi6Jianglin Fan7Jianglin Fan8Department of Molecular Pathology, Faculty of Medicine, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanDepartment of Molecular Pathology, Faculty of Medicine, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaDepartment of Molecular Pathology, Faculty of Medicine, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell, Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaInstitute for Experimental Animals, Kobe University School of Medicine, Kobe, JapanDepartment of Molecular Pathology, Faculty of Medicine, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaBackgroundIntracranial atherosclerosis (ICAS) is one of the most common causes of ischemic stroke, but there are few animal models that can recapitulate its pathological features. In this study, we examined ICAS pathological features and anatomic distributions using three types of hyperlipidemic rabbit models. We also investigated the effect of different lipoprotein profiles and hypertension on ICAS.Materials and MethodsWe examined Watanabe heritable hyperlipidemic (WHHL) rabbits, apoE knockout (KO) rabbits and wild-type rabbits (WT) fed a cholesterol diet, in addition to WT rabbits fed a standard diet as a control. The whole brain was dissected and embedded in paraffin. Serial sections were stained with either hematoxylin/eosin or elastica van Gieson, or immunohistochemically stained with monoclonal antibodies against macrophages and smooth muscle cells. We investigated (1) the presence of cerebral atherosclerosis; (2) the lesion locations in the cerebral arteries; (3) the degree of lumen stenosis; (4) pathological features and cellular components of the lesions in these rabbits; and (5) whether hypertension affects ICAS.ResultsICAS was detected in apoE and WHHL rabbits, but not in WT rabbits. Compared with apoE KO rabbits, WHHL rabbits had greater ICAS. The lesions of cerebral atherosclerosis were mainly distributed at the bifurcations of the posterior cerebral artery, basilar artery and vertebral artery, and they were basically characterized by smooth muscle cells and extracellular matrix with few macrophages. The extent of the ICAS in WHHL rabbits was significantly increased by hypertension.ConclusionsICAS was detected in WHHL and apoE KO rabbits, and occurred in specific locations in the cerebral arteries. Hypertension promotes the development of ICAS in the setting of hypercholesterolemia.https://www.frontiersin.org/articles/10.3389/fendo.2022.834207/fullatherosclerosiscerebral arterieshyperlipidemiahypertensionrabbits |
| spellingShingle | Xiangming Tang Manabu Niimi Huanjin Zhou Lu Chen Yajie Chen Haizhao Yan Masashi Shiomi Jianglin Fan Jianglin Fan Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models Frontiers in Endocrinology atherosclerosis cerebral arteries hyperlipidemia hypertension rabbits |
| title | Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models |
| title_full | Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models |
| title_fullStr | Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models |
| title_full_unstemmed | Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models |
| title_short | Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models |
| title_sort | pathological investigations of intracranial atherosclerosis using multiple hypercholesterolemic rabbit models |
| topic | atherosclerosis cerebral arteries hyperlipidemia hypertension rabbits |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.834207/full |
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