Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia
Background and aimsFatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1152124/full |
| _version_ | 1797856308563542016 |
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| author | Hanane Belhoul-Fakir Hanane Belhoul-Fakir Hanane Belhoul-Fakir Jiansha Wu Jiansha Wu Yen L. Yeow Gabrielle C. Musk Helen Kershaw Evan Ingley Evan Ingley Evan Ingley Bichen Sophie Zhao Bichen Sophie Zhao Christopher M. Reid Christopher M. Reid Christopher Lagat Brian Evans Peter L. Thompson Peter L. Thompson Michael L. Brown Juliana Hamzah Juliana Hamzah Juliana Hamzah Shirley Jansen Shirley Jansen Shirley Jansen Shirley Jansen |
| author_facet | Hanane Belhoul-Fakir Hanane Belhoul-Fakir Hanane Belhoul-Fakir Jiansha Wu Jiansha Wu Yen L. Yeow Gabrielle C. Musk Helen Kershaw Evan Ingley Evan Ingley Evan Ingley Bichen Sophie Zhao Bichen Sophie Zhao Christopher M. Reid Christopher M. Reid Christopher Lagat Brian Evans Peter L. Thompson Peter L. Thompson Michael L. Brown Juliana Hamzah Juliana Hamzah Juliana Hamzah Shirley Jansen Shirley Jansen Shirley Jansen Shirley Jansen |
| author_sort | Hanane Belhoul-Fakir |
| collection | DOAJ |
| description | Background and aimsFatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media.MethodsThree healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4–12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima.ResultsHigh lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima.ConclusionThe arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis. |
| first_indexed | 2024-04-09T20:38:21Z |
| format | Article |
| id | doaj.art-cc7b4b7dba8844d7a9cba2b43f51e6a6 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T20:38:21Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-cc7b4b7dba8844d7a9cba2b43f51e6a62023-03-30T06:44:38ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-03-011010.3389/fcvm.2023.11521241152124Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemiaHanane Belhoul-Fakir0Hanane Belhoul-Fakir1Hanane Belhoul-Fakir2Jiansha Wu3Jiansha Wu4Yen L. Yeow5Gabrielle C. Musk6Helen Kershaw7Evan Ingley8Evan Ingley9Evan Ingley10Bichen Sophie Zhao11Bichen Sophie Zhao12Christopher M. Reid13Christopher M. Reid14Christopher Lagat15Brian Evans16Peter L. Thompson17Peter L. Thompson18Michael L. Brown19Juliana Hamzah20Juliana Hamzah21Juliana Hamzah22Shirley Jansen23Shirley Jansen24Shirley Jansen25Shirley Jansen26Curtin Medical School, Curtin University, Bentley, Perth, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaHeart & Vascular Research Institute, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaHeart & Vascular Research Institute, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaAnimal Care Services, The University of Western Australia, Crawley, Perth, WA, AustraliaAnimal Care Services, The University of Western Australia, Crawley, Perth, WA, AustraliaDiscipline of Medical, Molecular, and Forensic Sciences, Murdoch University, Murdoch, WA, AustraliaSchool of Biomedical Sciences, Pharmacology, and Toxicology, The University of Western Australia, Perth, WA, AustraliaCentre for Medical Research, The University of Western Australia, Perth, WA, AustraliaCurtin Medical School, Curtin University, Bentley, Perth, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaSchool of Public Health and Preventive Medicine, Monash University, Clayton, VIC, AustraliaSchool of Population Health, Curtin University, Bentley, Perth, WA, Australia0Western Australia School of Mine: Minerals, Energy and Chemical Engineering, Curtin University, Kensington, Perth, WA, Australia0Western Australia School of Mine: Minerals, Energy and Chemical Engineering, Curtin University, Kensington, Perth, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaHeart & Vascular Research Institute, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, AustraliaSchool of Population Health, Curtin University, Bentley, Perth, WA, AustraliaCurtin Medical School, Curtin University, Bentley, Perth, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaHeart & Vascular Research Institute, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, AustraliaCurtin Medical School, Curtin University, Bentley, Perth, WA, AustraliaLaboratory of Targeted Drug Delivery, Imaging & Therapy, Harry Perkins Institute of Medical Research, QEII MedicalCentre, Nedlands, WA, AustraliaHeart & Vascular Research Institute, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia1Department of Vascular and Endovascular Surgery, Sir Charles Gairdner Hospital, Nedlands, Perth, WA, AustraliaBackground and aimsFatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media.MethodsThree healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4–12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima.ResultsHigh lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima.ConclusionThe arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1152124/fullatherogenesisatherosclerosisinflammationvascular smooth muscle cellatheromawall stress |
| spellingShingle | Hanane Belhoul-Fakir Hanane Belhoul-Fakir Hanane Belhoul-Fakir Jiansha Wu Jiansha Wu Yen L. Yeow Gabrielle C. Musk Helen Kershaw Evan Ingley Evan Ingley Evan Ingley Bichen Sophie Zhao Bichen Sophie Zhao Christopher M. Reid Christopher M. Reid Christopher Lagat Brian Evans Peter L. Thompson Peter L. Thompson Michael L. Brown Juliana Hamzah Juliana Hamzah Juliana Hamzah Shirley Jansen Shirley Jansen Shirley Jansen Shirley Jansen Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia Frontiers in Cardiovascular Medicine atherogenesis atherosclerosis inflammation vascular smooth muscle cell atheroma wall stress |
| title | Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| title_full | Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| title_fullStr | Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| title_full_unstemmed | Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| title_short | Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| title_sort | injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia |
| topic | atherogenesis atherosclerosis inflammation vascular smooth muscle cell atheroma wall stress |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1152124/full |
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