Abstract
This work analyzes the progressive stiffening of the aorta due to atherosclerosis development of both ApoE−/− and C57BL/6J mice fed on a Western (n = 5) and a normal (n = 5) chow diet for the ApoE−/− group and on a normal chow diet (n = 5) for the C57BL/6J group. Sets of 5 animals from the three groups were killed after 10, 20, 30 and 40 weeks on their respective diets (corresponding to 17, 27, 37 and 47 weeks of age). Mechanical properties (inflation test and axial residual stress measurements) and histological properties were compared for both strains, ApoE−/− on the hyper-lipidic diet and both ApoE−/− and C57BL/6J on the normal diet, after the same period and after different periods of diet. The results indicated that the aorta stiffness in the ApoE−/− and C57BL/6J mice under normal diet remained approximately constant irrespective of their age. However, the arterial stiffness in the ApoE−/− on the hyper-lipidic diet increased over time. Statistical differences were found between the group after 10 weeks and the groups after 30 and 40 weeks of a hyper-lipidic diet. Comparing the hyper-lipidic and normal diet mice, statistical differences were also found between both diets in all cases after 40 weeks of diet, frequently after 30 weeks, and in some cases after 20 weeks. The early stages of lesion corresponded to the first 2 weeks of diet. Advanced lesions were found at 30 weeks and, finally, the aorta was completely damaged after 40 weeks of diet. In conclusion, we found substantial changes in the mechanical properties of the aorta walls of the ApoE−/− mice fed with the hyper-lipidic diet compared to the normal chow diet groups for both the ApoE−/− and C57BL/6J groups. These findings could serve as a reference for the study of changes in the arterial wall properties in cases of atherosclerosis.
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References
Agianniotis, A., N. Stergiopulos. Wall properties of the apolipoprotein E-deficient mouse aorta. Atherosclerosis 223(2):314–320, 2012.
Buja, L. et al. Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 3(1):87–101, 1983.
Cardamone, L. et al. Origin of axial prestretch and residual stress in arteries. Biomech. Model. Mechanobiol. 8(6):431–446, 2009.
Carmeliet, P. et al. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat. Genet.17(4):439–444, 1997.
Chai, C.-K. et al. Compressive mechanical properties of atherosclerotic plaques. Indentation test to characterise the local anisotropic behaviour. J. Biomech. 47:784–792, 2014.
Chiu, J.-J., S. Chien. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91:327–387, 2011.
Daugherty, A. Mouse models of atherosclerosis. Am. J. Med. Sci. 323(1):3–10, 2002.
Davis, E. C. Elastic lamina growth in the developing mouse aorta. J. Histochem. Cytochem. 43(11):1115–1123, 1995.
Ebenstein, D. M. et al. Nanomechanical properties of calcification, fibrous tissue, and hematoma from atherosclerotic plaques. J. Biomed. Mater. Res. A 91:1028–1037, 2009.
Faggiotto, A. et al. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arterioscler. Thromb. Vasc. Biol. 4(4):323–340, 1984.
Gosling, R. G., M. M. Budge. Terminology for describing the elastic behavior of arteries. Hypertension 41:1180–1182, 2003.
Gotschy, A. et al. Local arterial stiffening assessed by MRI precedes atherosclerotic plaque formation. Circ. Cardiovasc. Imaging 6:916–923, 2013.
Greenwald, S. E. et al. Experimental investigation of the distribution of residual strains in the artery wall. ASME J. Biomech. Eng. 119(4):438–444, 1997.
Guo, X., G. S. Kassab. Variation of mechanical properties along the length of the aorta in C57BL/6 mice. Am. J. Physiol. Heart Circ. Physiol. 285:H2614–H2622, 2003.
Guo, X. et al. Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries. Am. J. Physiol. Heart Circ. Physiol. 291:H2354–H2361, 2006.
Hang, H. C., Y. C. Fung. Longitudinal strain of canine and porcine aortas. J. Biomech. 28:637–641, 1995.
Hayenga, H. et al. Regional atherosclerotic plaque properties in ApoE−/− mice quantified by atomic force, immunofluorescence, and light microscopy. J. Vasc. Res. 48:495–504, 2011.
Hirano, T. et al. Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E. Am. J. Physiol. - Endocrinol. Metab. 281(4):E665–E669, 2001.
Holzapfel, G. A. et al. Anisotropic mechanical properties of tissue components in human atherosclerotic plaques. ASME J. Biomech. Eng. 126:657–665, 2004.
Hoyt Jr., R. E. et al. The Mouse in Biomedical Research (2nd Edition). New York: Academic Press, 2007.
Huang, Y. et al. Axial nonuniformity of geometric and mechanical properties of mouse aorta is increased during postnatal growth. Am. J. Physiol. Heart Circ. Physiol. 290(2):H657–H664, 2006.
Jawien, J. et al. Mouse models of experimental atherosclerosis. J. Physiol. Pharmacol. 55(3):503–517, 2004.
Machii, M., A. E. Becker. Morphologic features of the normal aortic arch in neonates, infants, and children pertinent to growth. Ann. Thorac. Surg. 64(2):511–515, 1997.
Nakashima, Y. et al. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler. Thromb. Vasc. Biol. 14(1):133–140, 1994.
Ohayon, J. et al. Elucidating atherosclerotic vulnerable plaque rupture by modeling cross substitution of ApoE−/− mouse and human plaque components stiffnesses. Biomech. Model. Mechanobiol. 11:801–813, 2012.
Pelisek, J. et al. Neovascularization and angiogenic factors in advanced human carotid artery stenosis. Circ. J. 76(5):1274–1282, 2012.
Plump, A. et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71(2):343–353, 1992.
Reitman, J. et al. Yucatan miniature swine as a model for diet-induced atherosclerosis. Atherosclerosis 43(1):119–132, 1982.
Roach, M. R., A. C. Burton. The reason for the shape of the distensibility curves of arteries. Can. J. Biochem. Physiol. 35:681–690, 1957.
Ross, M. H., W. Pawlina. Histology: A Text and Atlas. New York: Churchill Livingstone, 2010.
Schwartz, C. J. et al. Aortic intimal monocyte recruitment in the normo and hypercholesterolemic baboon (Papio Cynocephalus). Virchows Arch. 405:175–191, 1985.
Taber, L. A. Nonlinear Theory of Elasticity. Applications in Biomechanics. River Edge, NJ: World Scientific Publishing Co., 2004
Teng, Z. et al. Material properties of components in human carotid atherosclerotic plaques: a uniaxial extension study. Acta Biomater. 10:5055–5063, 2014.
Tracqui, P. et al. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy. J. Struct. Biol. 174:115–123, 2011.
Villasana, L. et al. Dose- and ApoE isoform-dependent cognitive injury after cranial Fe-56 irradiation in female mice. Radiat. Res. 179(4):493–500, 2013.
Wagenseil, J. E. et al. The importance of elastin to aortic development in mice. Am. J. Physiol. Heart Circ. Physiol. 299:H257–H264, 2010.
Wagenseil, J. E. et al. Effects of elastin haploinsufficiency on the mechanical behavior of mouse arteries. Am. J. Physiol. Heart Circ. Physiol. 289:H1209–H1217, 2005.
Wagner, W. D. Risk factors in pigeons genetically selected for increased atherosclerosis susceptibility. Atherosclerosis 31(4):453–463, 1978.
Walsh, M. T. et al. Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques. J .Biomech. 47:793–804, 2014.
Wang, Y.-X. et al. Increased aortic stiffness assessed by pulse wave velocity in apolipoprotein E-deficient mice. Am. J. Physiol. - Heart Circ. Physiol. 278(2):H428–H434, 2000.
Weiss, J. A. et al. Deoxycorticosterone acetate salt hypertension in apolipoprotein E−/− mice results in accelerated atherosclerosis: the role of angiotensin II. Hypertension 51:218–24, 2008.
Wells, S. M. et al. Determinants of mechanical properties in the developing ovine thoracic aorta. Am. J. Physiol. - Heart Circ. Physiol. 277(4):H1385–H1391, 1999.
Wolinsky, H., S. Glagov. A lamellar unit of aortic medial structure and function in mammals. Circ. Res. 20(1):99–111, 1967.
Wong, L. C. Y., B. L. Langille. Developmental remodeling of the internal elastic lamina of rabbit arteries: effect of blood flow. Circ. Res. 78(5):799–805, 1996.
Zhang, S. H. et al. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Proc. Natl. Acad. Sci. USA 258(5081):468–471, 1992.
Acknowledgments
Support from the Spanish Ministry of Economy and Competitiveness through the research projects DPI2013-44391-P and PRI-AIBDE-2011-1216, the Department of Industry and Innovation (Government of Aragon) through the research group Grant T88 (Fondo Social Europeo) and from the University of Zaragoza through the research project UZ2008-BIO-21 is highly appreciated. The experimental tests have been performed by the ICTS “NANBIOSIS”, more specifically by the Tissue & Scaffold Characterization Unit (U13) of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN at the University of Zaragoza.
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Associate Editor Umberto Morbiducci oversaw the review of this article.
M. Cilla and M. M. Pérez have contributed equally to this work.
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Cilla, M., Pérez, M.M., Peña, E. et al. Effect of Diet and Age on Arterial Stiffening Due to Atherosclerosis in ApoE−/− Mice. Ann Biomed Eng 44, 2202–2217 (2016). https://doi.org/10.1007/s10439-015-1486-1
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DOI: https://doi.org/10.1007/s10439-015-1486-1