Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability
Objective: Characterization of the atherosclerotic process fully relies on histological evaluation and staging through a consensus grading system. So far, a head-to-head comparison of atherosclerotic process in experimental models and tissue resources commonly applied in atherosclerosis research wit...
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Elsevier
2023-01-01
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Series: | JVS - Vascular Science |
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author | Rogier A. van Dijk, MD, PhD Robert Kleemann, PhD Alexander F. Schaapherder, MD, PhD Antoon van den Bogaerdt, PhD Ulf Hedin, MD, PhD Ljubica Matic, PhD Jan H.N. Lindeman, MD, PhD |
author_facet | Rogier A. van Dijk, MD, PhD Robert Kleemann, PhD Alexander F. Schaapherder, MD, PhD Antoon van den Bogaerdt, PhD Ulf Hedin, MD, PhD Ljubica Matic, PhD Jan H.N. Lindeman, MD, PhD |
author_sort | Rogier A. van Dijk, MD, PhD |
collection | DOAJ |
description | Objective: Characterization of the atherosclerotic process fully relies on histological evaluation and staging through a consensus grading system. So far, a head-to-head comparison of atherosclerotic process in experimental models and tissue resources commonly applied in atherosclerosis research with the actual human atherosclerotic process is missing. Material and Methods: Aspects of the atherosclerotic process present in established murine atherosclerosis models and human carotid endarterectomy specimen were systematically graded using the modified American Heart Association histological classification (Virmani classification). Aspects were aligned with the atherosclerotic process observed in human coronary artery and aortic atherosclerosis reference tissues that were available through biobanks based on human tissue/organ donor material. Results: Apart from absent intraplaque hemorrhages in aortic lesions, the histological characteristics of the different stages of human coronary and aortic atherosclerosis are similar. Carotid endarterectomy samples all represent end-stage “fibrous calcified plaque” lesions, although secondary, progressive, and vulnerable lesions with gross morphologies similar to coronary/aortic lesions occasionally present along the primary lesions. For the murine lesions, clear histological parallels were observed for the intermediate lesion types (“pathological intimal thickening,” and “early fibroatheroma”). However, none of the murine lesions studied progressed to an equivalent of late fibroatheroma or beyond. Notable contrasts were observed for disease initiation: whereas disease initiation in humans is characterized by a mesenchymal cell influx in the intima, the earliest murine lesions are exclusively intimal, with subendothelial accumulation foam cells. A mesenchymal (and medial) response are absent. In fact, it is concluded that the stage of “adaptive intimal thickening” is absent in all mouse models included in this study. Conclusions: The Virmani classification for coronary atherosclerosis can be applied for systematically grading experimental and clinical atherosclerosis. Application of this histological grading tool shows clear parallels for intermediate human and murine atherosclerotic lesions. However, clear contrasts are observed for disease initiation, and late stage atherosclerotic lesions. Carotid endarterectomy all represent end-stage fibrous calcified plaque lesions, although secondary earlier lesions may present in a subset of samples. : Clinical Relevance: While murine models and (carotid) endarterectomy samples respectively experimental and clinical representatives of the atherosclerotic process, a head-to-head comparison of atherosclerotic with the actual human atherosclerotic process is missing. A systematically applied the revised American Heart Association (Virmani) classification on murine atherosclerosis models and carotid endarterectomy samples. Lesions present were aligned with coronary and peri-renal aortic reference samples that were obtained during organ/tissue donation. It is concluded that the Virmani classification for coronary atherosclerosis can be applied for systematically grading experimental and clinical atherosclerosis. Application of this histological grading tool shows clear parallels for the intermediate human and murine atherosclerotic lesions. However, major contrasts are observed for the process of disease initiation in humans and mice, and aspects of late stage atherosclerotic remained absent in the mouse models studies. It is concluded that carotid endarterectomy specimen all represent end-stage fibrous calcified plaque lesions, although secondary earlier lesions may occasionally present along the primary lesions. |
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spelling | doaj.art-1bddda1b4bf240c18304664ae53e7d632023-12-30T04:44:53ZengElsevierJVS - Vascular Science2666-35032023-01-014100118Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stabilityRogier A. van Dijk, MD, PhD0Robert Kleemann, PhD1Alexander F. Schaapherder, MD, PhD2Antoon van den Bogaerdt, PhD3Ulf Hedin, MD, PhD4Ljubica Matic, PhD5Jan H.N. Lindeman, MD, PhD6Department of Surgery, Leiden University Medical Center, Leiden, The NetherlandsThe Netherlands Organization for Applied Scientific Research (TNO), Department of Metabolic Health Research, TNO Metabolic Health Research, Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, Leiden, The NetherlandsMulti Tissue Center ETB-BISLIFE, Beverwijk, The NetherlandsDivision of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, SwedenDivision of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, SwedenDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Correspondence: Jan H.N. Lindeman, MD, PhD, Department of Vascular Surgery, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The NetherlandsObjective: Characterization of the atherosclerotic process fully relies on histological evaluation and staging through a consensus grading system. So far, a head-to-head comparison of atherosclerotic process in experimental models and tissue resources commonly applied in atherosclerosis research with the actual human atherosclerotic process is missing. Material and Methods: Aspects of the atherosclerotic process present in established murine atherosclerosis models and human carotid endarterectomy specimen were systematically graded using the modified American Heart Association histological classification (Virmani classification). Aspects were aligned with the atherosclerotic process observed in human coronary artery and aortic atherosclerosis reference tissues that were available through biobanks based on human tissue/organ donor material. Results: Apart from absent intraplaque hemorrhages in aortic lesions, the histological characteristics of the different stages of human coronary and aortic atherosclerosis are similar. Carotid endarterectomy samples all represent end-stage “fibrous calcified plaque” lesions, although secondary, progressive, and vulnerable lesions with gross morphologies similar to coronary/aortic lesions occasionally present along the primary lesions. For the murine lesions, clear histological parallels were observed for the intermediate lesion types (“pathological intimal thickening,” and “early fibroatheroma”). However, none of the murine lesions studied progressed to an equivalent of late fibroatheroma or beyond. Notable contrasts were observed for disease initiation: whereas disease initiation in humans is characterized by a mesenchymal cell influx in the intima, the earliest murine lesions are exclusively intimal, with subendothelial accumulation foam cells. A mesenchymal (and medial) response are absent. In fact, it is concluded that the stage of “adaptive intimal thickening” is absent in all mouse models included in this study. Conclusions: The Virmani classification for coronary atherosclerosis can be applied for systematically grading experimental and clinical atherosclerosis. Application of this histological grading tool shows clear parallels for intermediate human and murine atherosclerotic lesions. However, clear contrasts are observed for disease initiation, and late stage atherosclerotic lesions. Carotid endarterectomy all represent end-stage fibrous calcified plaque lesions, although secondary earlier lesions may present in a subset of samples. : Clinical Relevance: While murine models and (carotid) endarterectomy samples respectively experimental and clinical representatives of the atherosclerotic process, a head-to-head comparison of atherosclerotic with the actual human atherosclerotic process is missing. A systematically applied the revised American Heart Association (Virmani) classification on murine atherosclerosis models and carotid endarterectomy samples. Lesions present were aligned with coronary and peri-renal aortic reference samples that were obtained during organ/tissue donation. It is concluded that the Virmani classification for coronary atherosclerosis can be applied for systematically grading experimental and clinical atherosclerosis. Application of this histological grading tool shows clear parallels for the intermediate human and murine atherosclerotic lesions. However, major contrasts are observed for the process of disease initiation in humans and mice, and aspects of late stage atherosclerotic remained absent in the mouse models studies. It is concluded that carotid endarterectomy specimen all represent end-stage fibrous calcified plaque lesions, although secondary earlier lesions may occasionally present along the primary lesions.http://www.sciencedirect.com/science/article/pii/S2666350323000226Animal modelsAtherosclerosisCarotid endarterectomyComparison |
spellingShingle | Rogier A. van Dijk, MD, PhD Robert Kleemann, PhD Alexander F. Schaapherder, MD, PhD Antoon van den Bogaerdt, PhD Ulf Hedin, MD, PhD Ljubica Matic, PhD Jan H.N. Lindeman, MD, PhD Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability JVS - Vascular Science Animal models Atherosclerosis Carotid endarterectomy Comparison |
title | Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability |
title_full | Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability |
title_fullStr | Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability |
title_full_unstemmed | Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability |
title_short | Validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue: similarities but profound differences in disease initiation and plaque stability |
title_sort | validating human and mouse tissues commonly used in atherosclerosis research with coronary and aortic reference tissue similarities but profound differences in disease initiation and plaque stability |
topic | Animal models Atherosclerosis Carotid endarterectomy Comparison |
url | http://www.sciencedirect.com/science/article/pii/S2666350323000226 |
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