Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia
Introduction: Rodent models of cardiovascular disease have uncovered various types of lymphatic vessel dysfunction that occur in association with atherosclerosis, type II diabetes and obesity. Previously, we presented in vivo evidence for impaired lymphatic drainage in apolipoprotein E null (ApoE−/−...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.1098408/full |
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| author | Michael J. Davis Joshua P. Scallan Jorge A. Castorena-Gonzalez Hae Jin Kim Lim Hwee Ying Yeo Kim Pin Yeo Kim Pin Veronique Angeli Veronique Angeli |
| author_facet | Michael J. Davis Joshua P. Scallan Jorge A. Castorena-Gonzalez Hae Jin Kim Lim Hwee Ying Yeo Kim Pin Yeo Kim Pin Veronique Angeli Veronique Angeli |
| author_sort | Michael J. Davis |
| collection | DOAJ |
| description | Introduction: Rodent models of cardiovascular disease have uncovered various types of lymphatic vessel dysfunction that occur in association with atherosclerosis, type II diabetes and obesity. Previously, we presented in vivo evidence for impaired lymphatic drainage in apolipoprotein E null (ApoE−/−) mice fed a high fat diet (HFD). Whether this impairment relates to the dysfunction of collecting lymphatics remains an open question. The ApoE−/− mouse is a well-established model of cardiovascular disease, in which a diet rich in fat and cholesterol on an ApoE deficient background accelerates the development of hypercholesteremia, atherosclerotic plaques and inflammation of the skin and other tissues. Here, we investigated various aspects of lymphatic function using ex vivo tests of collecting lymphatic vessels from ApoE+/+ or ApoE−/− mice fed a HFD.Methods: Popliteal collectors were excised from either strain and studied under defined conditions in which we could quantify changes in lymphatic contractile strength, lymph pump output, secondary valve function, and collecting vessel permeability.Results: Our results show that all these aspects of lymphatic vessel function are altered in deleterious ways in this model of hypercholesterolemia.Discussion: These findings extend previous in vivo observations suggesting significant dysfunction of lymphatic endothelial cells and smooth muscle cells from collecting vessels in association with a HFD on an ApoE-deficient background. An implication of our study is that collecting vessel dysfunction in this context may negatively impact the removal of cholesterol by the lymphatic system from the skin and the arterial wall and thereby exacerbate the progression and/or severity of atherosclerosis and associated inflammation. |
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| id | doaj.art-42b478dcfd204ab7b7e753a2af8ee235 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-11T00:37:55Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-42b478dcfd204ab7b7e753a2af8ee2352023-01-06T14:07:22ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-01-011310.3389/fphys.2022.10984081098408Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemiaMichael J. Davis0Joshua P. Scallan1Jorge A. Castorena-Gonzalez2Hae Jin Kim3Lim Hwee Ying4Yeo Kim Pin5Yeo Kim Pin6Veronique Angeli7Veronique Angeli8Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesDepartment of Molecular Pharmacology, University of South Florida, Tampa, FL, United StatesDepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA, United StatesDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesImmunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeImmunology Programme, Life Sciences Institute, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology and Immunology, National University of Singapore, Singapore, SingaporeImmunology Programme, Life Sciences Institute, National University of Singapore, Singapore, SingaporeIntroduction: Rodent models of cardiovascular disease have uncovered various types of lymphatic vessel dysfunction that occur in association with atherosclerosis, type II diabetes and obesity. Previously, we presented in vivo evidence for impaired lymphatic drainage in apolipoprotein E null (ApoE−/−) mice fed a high fat diet (HFD). Whether this impairment relates to the dysfunction of collecting lymphatics remains an open question. The ApoE−/− mouse is a well-established model of cardiovascular disease, in which a diet rich in fat and cholesterol on an ApoE deficient background accelerates the development of hypercholesteremia, atherosclerotic plaques and inflammation of the skin and other tissues. Here, we investigated various aspects of lymphatic function using ex vivo tests of collecting lymphatic vessels from ApoE+/+ or ApoE−/− mice fed a HFD.Methods: Popliteal collectors were excised from either strain and studied under defined conditions in which we could quantify changes in lymphatic contractile strength, lymph pump output, secondary valve function, and collecting vessel permeability.Results: Our results show that all these aspects of lymphatic vessel function are altered in deleterious ways in this model of hypercholesterolemia.Discussion: These findings extend previous in vivo observations suggesting significant dysfunction of lymphatic endothelial cells and smooth muscle cells from collecting vessels in association with a HFD on an ApoE-deficient background. An implication of our study is that collecting vessel dysfunction in this context may negatively impact the removal of cholesterol by the lymphatic system from the skin and the arterial wall and thereby exacerbate the progression and/or severity of atherosclerosis and associated inflammation.https://www.frontiersin.org/articles/10.3389/fphys.2022.1098408/fulllymphatic valvepermeabilitycontractile dysfunctionhigh fat dietback-leakpump limit |
| spellingShingle | Michael J. Davis Joshua P. Scallan Jorge A. Castorena-Gonzalez Hae Jin Kim Lim Hwee Ying Yeo Kim Pin Yeo Kim Pin Veronique Angeli Veronique Angeli Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia Frontiers in Physiology lymphatic valve permeability contractile dysfunction high fat diet back-leak pump limit |
| title | Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia |
| title_full | Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia |
| title_fullStr | Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia |
| title_full_unstemmed | Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia |
| title_short | Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia |
| title_sort | multiple aspects of lymphatic dysfunction in an apoe mouse model of hypercholesterolemia |
| topic | lymphatic valve permeability contractile dysfunction high fat diet back-leak pump limit |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.1098408/full |
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