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Abstract

First, we would like to acknowledge our colleagues from Zhengzhou University for their kind comments on our experimental study. We have shown the beneficial effect of leukocyte elastase inhibition in an experimental model of aneurysm in rats, in which enhancement of neutrophil activation in the intraluminal thrombus (ILT) was obtained by repeated injections of weak pathogens.1Delbosc S, Rouer M, Alsac JM, Louedec L, Philippe M, Meilhac O, et al. Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms [Published online ahead of print August 28, 2014]. J Vasc Surg. http://dx.doi.org/10.1016/j.jvs.2014.07.102.Google Scholar We agree that elastin and collagen contents could represent end points for the beneficial effects of elastase inhibition by AZD9668, although we did not specifically report this in our study. In our concept of human abdominal aortic aneurysm (AAA) pathology and of experimental models, we proposed that the biological activities of the ILT play a major role in the evolution of aneurysmal dilation due to the outward convection across the aneurysmal wall of proteolytic enzymes (mainly plasmin and elastase) generated within the ILT.2Houard X. Rouzet F. Touat Z. Philippe M. Dominguez M. Fontaine V. et al.Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms.J Pathol. 2007; 212: 20-28Crossref PubMed Scopus (98) Google Scholar Contrasting with the detrimental pathologic outcome of human AAA, experimental models spontaneously evolve toward healing by stromal cell colonization of the ILT and, therefore, to the stabilization of the AAA. In murine species, including rats and mice, the white blood cell count is inversed compared with humans. In man, neutrophils represent 60% to 70% of circulating leukocytes, whereas they represent only ∼10% of total leukocytes in rats and mice (http://www.informatics.jax.org/greenbook/frames/frame17.shtml). This relative lack of neutrophils is probably related to interleukin 8 gene deletion in the murine species.3Modi W.S. Yoshimura T. Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals.Mol Biol Evol. 1999; 16: 180-193Crossref PubMed Scopus (82) Google Scholar This may partly explain why the ILT tends to become a good substrate for cellular healing in murine experimental models. In this context, repeated injections of weak pathogens and their preferential accumulation in the ILT prevented the healing process. This is why we focused our study on the healing or detrimental biology of the ILT rather than on the extracellular matrix of the aneurysmal wall. We read with interest the study of Bi et al4Bi Y, Zhong H, Xu K, Qi X, Zhang Z, Wu G, et al. Novel experimental model of enlarging abdominal aortic aneurysm in rabbits [Published online ahead of print, April 10, 2014]. J Vasc Surg. http://dx.doi.org/10.1016/j.jvs.2014.02.062.Google Scholar describing a new model of AAA in rabbits, associating elastase infusion and mechanical stenosis. We agree that hemorheologic changes are important in AAA pathophysiology, involving mainly ILT formation and progression associated with changes of outward mass transport through the wall.5Biasetti J. Spazzini P.G. Swedenborg J. Gasser T.C. An integrated fluid-chemical model toward modeling the formation of intra-luminal thrombus in abdominal aortic aneurysms.Front Physiol. 2012; 3: 266Crossref PubMed Scopus (49) Google Scholar The best demonstration of this hemorheologic role in humans was made by Vollmar et al6Vollmar J.F. Paes E. Pauschinger P. Henze E. Friesch A. Aortic aneurysms as late sequelae of above-knee amputation.Lancet. 1989; 2: 834-835Abstract PubMed Scopus (84) Google Scholar in their remarkable clinical investigation showing the relationship between asymmetric flow induced by above-knee amputation and the increased frequency of AAA development in male war veterans. Regarding “Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms”Journal of Vascular SurgeryVol. 62Issue 5PreviewWe read with interest the important article by Delbosc et al,1 published on August 28, 2014 in Journal of Vascular Surgery, documenting that AZD9668 treatment could prevent rat abdominal aortic aneurysm (AAA). Previously, they reported that neutrophil recruitment and activation plays a major role in AAA growth and confirmed it by using elastase perfusion AAA, followed by repeated injection of Porphyromonas gingivalis.2 We are quite interested in this novel AAA model, in which repeated injections of P gingivalis prevented the spontaneous healing of rat AAA. Full-Text PDF Open Archive