Histological evaluation of the aortic wall response following endovascular aneurysm repair and endovascular aneurysm sealing

Objective: The Nellix endovascular aneurysm sealing (EVAS) system was developed as an alternative to conventional endovascular aneurysm repair (EVAR) to minimize endoleaks. A significantly higher failure rate of EVAS may be related to an interaction between the filled endobags and the AAA wall. In general, biological information on aortic remodeling after traditional EVAR is scarce. In this light, we provide here the first histologic evaluation of aneurysm wall morphology after EVAR and EVAS. Methods: Fourteen histological human wall samples of EVAS and EVAR explantation were systematically analysed. Primary open aorta repair samples were included as reference. Results: Compared with primary open aortic repair samples, endovascular repair aortic samples were characterized by more pronounced fibrosis, a greater number of ganglionic structures, decreased cellular inflammation, less calcification, and a lower atherosclerotic load. EVAS was specifically associated with the presence of unstructured elastin deposits. Conclusions: The biological response of the aortic wall after endovascular repair resembles the maturation process of a scar rather than a bona fide healing response. Moreover, the inflammatory response in the aortic wall after placement of endovascular protheses is less prominent than after primary open repair. A specific post-EVAS aortic wall characteristic was unstructured elastin fragments

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 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