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, vol. 4, pp. 100118
Abstract
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.
Authors 7
-
Leiden University Medical Center · Isala
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Current address: Dept Radiology, Isala Hospital, Zwolle, The Netherlands
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
-
Netherlands Organisation for Applied Scientific Research
Affiliation as printed
The Netherlands Organization for Applied Scientific Research (TNO), Department of Metabolic Health Research, TNO Metabolic Health Research, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
-
Affiliation as printed
Multi Tissue Center ETB-BISLIFE, Beverwijk, The Netherlands
-
Affiliation as printed
Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
-
Affiliation as printed
Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
-
Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
Cited by 6 stored of 6
6 results
No patents citing this paper on Lens.org (checked 2026-10-11).