LETTERS TO THE EDITOR
Regarding “Novel experimental model of enlarging abdominal aortic aneurysm in rabbits”
4. Yamaguchi T, Yokokawa M, Suzuki M, Higashide S, Katoh Y, Sugiyama S, et al. The time course of elastin fiber degeneration in a rat aneurysm model. Surg Today 2000;30:727-31.
The article by Bi et al,1 published on April 10, 2014, in the Journal of Vascular Surgery, provides a novel model of an enlarging abdominal aortic aneurysm (AAA) in rabbits to overcome the self-healing phenomenon reported by Origuchi et al.2 Previously, the authors modified the rabbit AAA by application of a higher concentration of elastase3; however, it returns to morphologic normality #5 months. Matrix metalloproteinases (MMPs) play a vital role in AAA formation. Elastase-induced AAA developed after an infusion of elastase because of an inflammatory cascade that ultimately results in matrix destruction by MMPs. This model indicates that MMPs play a “bad” even “evil” role in the formation of AAA, and many researchers try to prevent or regress AAA by inhibiting MMPs. However, AAA formation in the rat had nothing to do with endogenous MMPs produced by the infiltrating cells but was due to the exogenously infused elastase itself.4 This finding was confirmed in the rabbit model. The aortic walls showed marked medial attenuation, and the medial elastins had almost completely dissolved on day 0.2 The rabbit AAA formed only when the aorta was degenerated dramatically by a high concentration of elastase.3 Interestingly, the rabbit AAA formed and enlarged progressively after a low concentration elastase incubation and aortic coarctation.1 We thus hypothesize that murine or rabbit AAA form mainly due to the matrix destruction by exogenous elastase rather than to endogenous MMPs. Strong MMP9 staining and macrophages were found throughout the aneurysm wall #1 week, and both expressions decreased thereafter.3 Inflammatory cell infiltration and MMP9 expression are likely to be a result of the degeneration of the aortic wall.4 Smooth muscle cells showed a moderate expression of MMP2 during a 5-month follow-up. Similar expressions were seen in this enlarging AAA model, and it seems that hemodynamic change caused by coarctation is vital to the progression of rabbit AAA rather than endogenous MMPs. Endogenous MMPs may play a positive role in remodeling of aneurysmal wall and cause the self-healing process of elastase-induced aneurysm.
http://dx.doi.org/10.1016/j.jvs.2014.12.011
Hongmei Chen, MD Yuanyuan Yan, MD Zhan Ma, MD Feng Kong, MD Department of Ultrasound Zhengzhou Central Hospital Affliated to Zhengzhou University Zhengzhou, China E-mail: [email protected] REFERENCE 1. Bi Y, Zhong H, Xu K, Qi X, Zhang Z, Wu G, et al. Novel experimental model of enlarging abdominal aortic aneurysm in rabbits. J Vasc Surg 2015;62:1054-63. 2. Origuchi N, Shigematsu H, Izumiyama N, Nakamura K, Toku A, Muto T. Aneurysm induced by periarterial application of elastase heals spontaneously. Int Angiol 1998;17:113-9. 3. Bi Y, Zhong H, Xu K, Ni Y, Qi X, Zhang Z, et al. Performance of a modified rabbit model of abdominal aortic aneurysm induced by topical application of porcine elastase: 5-month follow-up study. Eur J Vasc Endovasc Surg 2013;45:145-52.
Reply We appreciate the letter from Kong et al regarding our article. To some extent, we agree with their hypothesis that the abdominal aortic aneurysm (AAA) formed mainly due to the matrix destruction by exogenous elastase and that endogenous matrix metalloproteinases (MMPs) play a positive role in remodeling of aneurysmal wall, which causes a self-healing phenomenon in the rabbit elastase-induced AAA. In this model, exogenous elastase infusion is essential for the induction of endogenous MMPs, which causes matrix destruction and aneurysm formation. Thus, studies try to break this “vicious circle” by inhibiting MMPs. We previously modified the rabbit AAA by several means, without satisfactory outcomes.1-3 The lower concentration of elastase incubation for 30 minutes was unable to induce AAA formation2; however, enlarging AAA developed once it combined with hemodynamics.4 In the novel enlarging model, hemodynamic changes may play a vital role in the formation and progression of the AAA, and MMPs are essential for the aneurysmal remodeling. Of note, our results did not evaluate quantitatively, and further quantitative analysis is wanted. Anyway, this enlarging model appropriately mimics human AAA disease and may be valuable for elucidating AAA mechanisms and therapeutic interventions in animal studies. Yonghua Bi, MD, PhD Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou, China Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of China Medical University Shenyang, China Xinwei Han, MD, PhD Department of Interventional Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou, China E-mail: [email protected] Hongshan Zhong, MD, PhD Ke Xu, MD, PhD Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of China Medical University Shenyang, China REFERENCES 1. Bi Y, Xu K, Zhong H, Qi X, Zhang Z, Ni Y. A novel in vivo rabbit model of abdominal aortic aneurysm induced by periarterial incubation of papain. J Vasc Interv Radiol 2012;23:1529-36.
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Regarding “Novel experimental model of enlarging abdominal aortic aneurysm in rabbits”
4. Yamaguchi T, Yokokawa M, Suzuki M, Higashide S, Katoh Y, Sugiyama S, et al. The time course of elastin fiber degeneration in a rat aneurysm model. Surg Today 2000;30:727-31.
The article by Bi et al,1 published on April 10, 2014, in the Journal of Vascular Surgery, provides a novel model of an enlarging abdominal aortic aneurysm (AAA) in rabbits to overcome the self-healing phenomenon reported by Origuchi et al.2 Previously, the authors modified the rabbit AAA by application of a higher concentration of elastase3; however, it returns to morphologic normality #5 months. Matrix metalloproteinases (MMPs) play a vital role in AAA formation. Elastase-induced AAA developed after an infusion of elastase because of an inflammatory cascade that ultimately results in matrix destruction by MMPs. This model indicates that MMPs play a “bad” even “evil” role in the formation of AAA, and many researchers try to prevent or regress AAA by inhibiting MMPs. However, AAA formation in the rat had nothing to do with endogenous MMPs produced by the infiltrating cells but was due to the exogenously infused elastase itself.4 This finding was confirmed in the rabbit model. The aortic walls showed marked medial attenuation, and the medial elastins had almost completely dissolved on day 0.2 The rabbit AAA formed only when the aorta was degenerated dramatically by a high concentration of elastase.3 Interestingly, the rabbit AAA formed and enlarged progressively after a low concentration elastase incubation and aortic coarctation.1 We thus hypothesize that murine or rabbit AAA form mainly due to the matrix destruction by exogenous elastase rather than to endogenous MMPs. Strong MMP9 staining and macrophages were found throughout the aneurysm wall #1 week, and both expressions decreased thereafter.3 Inflammatory cell infiltration and MMP9 expression are likely to be a result of the degeneration of the aortic wall.4 Smooth muscle cells showed a moderate expression of MMP2 during a 5-month follow-up. Similar expressions were seen in this enlarging AAA model, and it seems that hemodynamic change caused by coarctation is vital to the progression of rabbit AAA rather than endogenous MMPs. Endogenous MMPs may play a positive role in remodeling of aneurysmal wall and cause the self-healing process of elastase-induced aneurysm.
http://dx.doi.org/10.1016/j.jvs.2014.12.011
Hongmei Chen, MD Yuanyuan Yan, MD Zhan Ma, MD Feng Kong, MD Department of Ultrasound Zhengzhou Central Hospital Affliated to Zhengzhou University Zhengzhou, China E-mail: [email protected] REFERENCE 1. Bi Y, Zhong H, Xu K, Qi X, Zhang Z, Wu G, et al. Novel experimental model of enlarging abdominal aortic aneurysm in rabbits. J Vasc Surg 2015;62:1054-63. 2. Origuchi N, Shigematsu H, Izumiyama N, Nakamura K, Toku A, Muto T. Aneurysm induced by periarterial application of elastase heals spontaneously. Int Angiol 1998;17:113-9. 3. Bi Y, Zhong H, Xu K, Ni Y, Qi X, Zhang Z, et al. Performance of a modified rabbit model of abdominal aortic aneurysm induced by topical application of porcine elastase: 5-month follow-up study. Eur J Vasc Endovasc Surg 2013;45:145-52.
Reply We appreciate the letter from Kong et al regarding our article. To some extent, we agree with their hypothesis that the abdominal aortic aneurysm (AAA) formed mainly due to the matrix destruction by exogenous elastase and that endogenous matrix metalloproteinases (MMPs) play a positive role in remodeling of aneurysmal wall, which causes a self-healing phenomenon in the rabbit elastase-induced AAA. In this model, exogenous elastase infusion is essential for the induction of endogenous MMPs, which causes matrix destruction and aneurysm formation. Thus, studies try to break this “vicious circle” by inhibiting MMPs. We previously modified the rabbit AAA by several means, without satisfactory outcomes.1-3 The lower concentration of elastase incubation for 30 minutes was unable to induce AAA formation2; however, enlarging AAA developed once it combined with hemodynamics.4 In the novel enlarging model, hemodynamic changes may play a vital role in the formation and progression of the AAA, and MMPs are essential for the aneurysmal remodeling. Of note, our results did not evaluate quantitatively, and further quantitative analysis is wanted. Anyway, this enlarging model appropriately mimics human AAA disease and may be valuable for elucidating AAA mechanisms and therapeutic interventions in animal studies. Yonghua Bi, MD, PhD Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou, China Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of China Medical University Shenyang, China Xinwei Han, MD, PhD Department of Interventional Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou, China E-mail: [email protected] Hongshan Zhong, MD, PhD Ke Xu, MD, PhD Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology The First Affiliated Hospital of China Medical University Shenyang, China REFERENCES 1. Bi Y, Xu K, Zhong H, Qi X, Zhang Z, Ni Y. A novel in vivo rabbit model of abdominal aortic aneurysm induced by periarterial incubation of papain. J Vasc Interv Radiol 2012;23:1529-36.
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