Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study
Rationale: While high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cardiovascular events, it is still unclear whether familial hypercholesterolemia (FH) and Tangier’s disease (TD), caused by mutations...
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MDPI AG
2019-09-01
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| Series: | Cells |
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| author | Lili Wei Haozhe Shi Xiao Lin Xin Zhang Yuhui Wang George Liu Xunde Xian |
| author_facet | Lili Wei Haozhe Shi Xiao Lin Xin Zhang Yuhui Wang George Liu Xunde Xian |
| author_sort | Lili Wei |
| collection | DOAJ |
| description | Rationale: While high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cardiovascular events, it is still unclear whether familial hypercholesterolemia (FH) and Tangier’s disease (TD), caused by mutations in LDLR and ABCA1, respectively, influence ischemic stroke (IS) in humans. Objective: We sought to establish an easier, more effective, and time-saving method to induce IS, then studied the precise effects of different types of lipoproteins on IS. Methods and Results: A new technique termed contralateral middle cerebral artery occlusion (c-MCAO) was introduced to human-like hamster models to induce IS. Compared to traditional distal MCAO (d-MCAO) induced by electrocoagulation, c-MCAO resulted in a more severe IS with larger infarct sizes and more blood−brain barrier (BBB) disruption after 24 h. It was shown that c-MCAO markedly elicited an increase in brain infarct volume and BBB leakage in both homozygous LDLR (LDLR<sup>−/−</sup>) and ABCA1 knockout (ABCA1<sup>−/−</sup>) hamsters, but not in heterozygous LDLR knockout (LDLR<sup>+/−</sup>) hamsters when compared to wild-type (WT) controls. Conclusions: Using human-like genetically engineered hamsters, our findings demonstrated that both high LDL-C level caused by homozygous LDLR deficiency and severe low HDL-C level caused by deleting ABCA1 were risk factors of IS. As such, we believe the development of this novel IS hamster model is suitable for future ischemic/reperfusion studies. |
| first_indexed | 2024-03-12T08:23:04Z |
| format | Article |
| id | doaj.art-c6b3c1cd788443788bb6b2f96305414a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:23:04Z |
| publishDate | 2019-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-c6b3c1cd788443788bb6b2f96305414a2023-09-02T18:21:27ZengMDPI AGCells2073-44092019-09-0189102810.3390/cells8091028cells8091028Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke StudyLili Wei0Haozhe Shi1Xiao Lin2Xin Zhang3Yuhui Wang4George Liu5Xunde Xian6Key Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaHebei Invivo Biotech Co, Shijiazhuang 050000, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, ChinaRationale: While high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cardiovascular events, it is still unclear whether familial hypercholesterolemia (FH) and Tangier’s disease (TD), caused by mutations in LDLR and ABCA1, respectively, influence ischemic stroke (IS) in humans. Objective: We sought to establish an easier, more effective, and time-saving method to induce IS, then studied the precise effects of different types of lipoproteins on IS. Methods and Results: A new technique termed contralateral middle cerebral artery occlusion (c-MCAO) was introduced to human-like hamster models to induce IS. Compared to traditional distal MCAO (d-MCAO) induced by electrocoagulation, c-MCAO resulted in a more severe IS with larger infarct sizes and more blood−brain barrier (BBB) disruption after 24 h. It was shown that c-MCAO markedly elicited an increase in brain infarct volume and BBB leakage in both homozygous LDLR (LDLR<sup>−/−</sup>) and ABCA1 knockout (ABCA1<sup>−/−</sup>) hamsters, but not in heterozygous LDLR knockout (LDLR<sup>+/−</sup>) hamsters when compared to wild-type (WT) controls. Conclusions: Using human-like genetically engineered hamsters, our findings demonstrated that both high LDL-C level caused by homozygous LDLR deficiency and severe low HDL-C level caused by deleting ABCA1 were risk factors of IS. As such, we believe the development of this novel IS hamster model is suitable for future ischemic/reperfusion studies.https://www.mdpi.com/2073-4409/8/9/1028LDLRABCA1gold syrian hamsterischemic stroke |
| spellingShingle | Lili Wei Haozhe Shi Xiao Lin Xin Zhang Yuhui Wang George Liu Xunde Xian Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study Cells LDLR ABCA1 gold syrian hamster ischemic stroke |
| title | Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study |
| title_full | Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study |
| title_fullStr | Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study |
| title_full_unstemmed | Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study |
| title_short | Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study |
| title_sort | impact of cholesterol on ischemic stroke in different human like hamster models a new animal model for ischemic stroke study |
| topic | LDLR ABCA1 gold syrian hamster ischemic stroke |
| url | https://www.mdpi.com/2073-4409/8/9/1028 |
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