Aorta transplantation in young apolipoprotein E-deficient mice: Possible model for studies on regression of atherosclerotic lesions?

• Authors: Zbyněk Tonar , Dagmar Bobková , Kirsti Witter , Vít Matějka , Jana Havlíčková , Věra Lánská , Rudolf Poledne
• Languages of publication: EN

Abstracts

EN

Syngeneic transplantation of murine aorta segments with advanced atherosclerotic lesions in defined recipients is a valuable model for regression studies. To date, this model has not been used to study the regression of initial atherosclerotic lesions. The aim of this study was to evaluate a microsurgical technique of syngeneic heterotopic transplantation of the thoracic aorta of young apolipoprotein E-deficient (ApoE-/-) mice to the abdominal aorta of wild-type recipients. Stereological quantification methods were tested in order to assess changes in structure and volume of the aortic wall including the involvement of immune cells in changes of the atherosclerotic lesions. The animals were euthanised one month after surgery and histological analysis including stereological quantification of changes in both the grafts and adjacent aorta segments was performed. The overall survival rate of the recipients was 62.5%. No regression of initial atherosclerotic lesion was achieved and neointima formation and elastin degradation prevailed in all transplanted specimens. The volume of the arteriosclerotic lesions was higher (p<0.001) and elastin length density was lower (p<0.001) in transplanted ApoE-/- samples as compared to adjacent segments. In transplanted grafts, T- and B-lymphocytes, macrophages and neutrophilic granulocytes formed non-random clusters within the vessel wall and they were colocalised with the sutures. The reproducibility of the promising regression model was derogated in young mice by the striking dependence of the results upon the operation technique. Stereological assessment has proven to be accurate, correct and reproducible; it has provided us with robust quantitative estimates, which can be achieved with a reasonable effort.

Keywords

EN

Heterotopic transplantation; Quantitative histology; Stereology

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2010
• Volume: 5
• Issue: 3
• Pages: 280-291

Dates

published

1 - 6 - 2010

online

9 - 4 - 2010

Contributors

author

Zbyněk Tonar

author

Dagmar Bobková

• Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague, Czech Republic

author

Kirsti Witter

• Institute of Histology and Embryology, Department of Pathobiology, University of Veterinary Medicine, Veterinärplatz 1, A-1210, Vienna, Austria

author

Vít Matějka

• Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, Karlovarská 48, 301 66, Pilsen, Czech Republic

author

Jana Havlíčková

• Laboratory of Pathophysiology of Cardiovascular System, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague, Czech Republic

author

Věra Lánská

• Statistics Unit, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague, Czech Republic

author

Rudolf Poledne

• Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague, Czech Republic

References

• [1] Plump A.S., Smith J.D., Hayek T., Aalto-Setala K., Walsh A., Verstuyft J.G., Rubin E.M., Breslow J.L. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E- deficient mice created by homologous recombination in ES cells. Cell, 1992, 71,343–353 http://dx.doi.org/10.1016/0092-8674(92)90362-G[Crossref]
• [2] Breslow J.L. Transgenic mouse model of lipoprotein metabolism and atherosclerosis. PNAS, 1993, 90, 8314–8318 http://dx.doi.org/10.1073/pnas.90.18.8314[Crossref]
• [3] Breslow J.L. Mouse models of atherosclerosis. Science 1996, 272, 685–688 http://dx.doi.org/10.1126/science.272.5262.685[Crossref]
• [4] von Eckardstein A. Cholesterol efflux from macrophages and other cells. Curr. Opin. Lipidol., 1996, 7, 308–319 http://dx.doi.org/10.1097/00041433-199610000-00009[Crossref]
• [5] Curtiss L.K. ApoE in atherosclerosis: A protein with multiple hats. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 1852–1853 [Crossref]
• [6] Greenow K., Pearce N.J., Ramji D.P. The key role of apolipoprotein E in atherosclerosis. J. Mol. Med., 2005, 83, 329–342. http://dx.doi.org/10.1007/s00109-004-0631-3[Crossref]
• [7] van Ree J.H., van den Broek W.J., Dahlmans V.E., Groot P.H., Vidgeon-Hart M., Frants R.R., Wieringa B., Havekes L.M., Hofker M.H. Dietinduced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice. Atherosclerosis, 1994, 111, 25–37 http://dx.doi.org/10.1016/0021-9150(94)90188-0[Crossref]
• [8] Nakashima Y., Plump A.S., Raines E.W., Breslow J.L., Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler. Thromb. Vasc. Biol., 1994, 14, 133–140 [Crossref]
• [9] Jawien J., Nastalek P., Korbut R. Mouse models of experimental atherosclerosis. J. Physiol. Pharmacol., 2004, 55, 503–517
• [10] Ohashi R., Mu H., Yao Q., Chen C. Cellular and molecular mechanisms of atherosclerosis with mouse models. Trends Cardiovasc. Med., 2004, 14, 187–190 http://dx.doi.org/10.1016/j.tcm.2004.04.002[Crossref]
• [11] Garber D.W., Kulkarni K.R., Anantharamaiah G.M. A sensitive and convenient method for lipoprotein profile analysis of individual mouse plasma samples. J. Lip. Res., 2000, 41, 1020–1026
• [12] Havel R.J., Eder H.A., Bragdon J.H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest., 1955, 34, 1345–1353 http://dx.doi.org/10.1172/JCI103182[Crossref]
• [13] Gotto A.M. Jr., Pownall H.J., Havel R.J. Introduction to the Plasma Lipoproteins. In: Segrest J.P., Albers J.J. (Eds.), Methods in Enzymology, Vol. 128. Plasma Lipoproteins. Part A. Preparation, Structure, and Molecular Biology Academic Press, Orlando, 1986
• [14] Shi W., Wang X,, Wang N.J., McBride W.H., Lusis A.J. Effect of macrophage-derived apolipoprotein E on established atherosclerosis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 2261–2266 [Crossref]
• [15] van Eck M., Herijgers N., van Dijk K.W., Havekes L.M., Hofker M.H., Groot P.H., van Berkel T.J. Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2, (Arg158->Cys) on cholesterol levels and atherosclerosis in ApoEdeficient mice. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 119–127
• [16] Gough P.J., Raines E.W. Gene therapy of apolipoprotein E-deficient mice using a novel macrophage-specific retroviral vector. Blood, 2003, 101, 485–491 http://dx.doi.org/10.1182/blood-2002-07-2131[Crossref]
• [17] Su Y.R., Ishiguro H., Major A.S., Dove D.E., Zhang W., Hasty A.H., Babaev V.R., Linton M.F., Fazio S. Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters. Mol. Ther., 2003, 8, 576–583 http://dx.doi.org/10.1016/S1525-0016(03)00214-4[Crossref]
• [18] Reis E.D., Li J., Fayad Z.A., Rong J.X., Hansoty D., Aguinaldo J.G., Fallon J.T., Fisher E.A. Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model. J. Vasc. Surg., 2001, 34, 541–547 http://dx.doi.org/10.1067/mva.2001.115963[Crossref]
• [19] Rong J.X., Li J., Reis E.D., Choudhury R.P., Dansky H.M., Elmalem V.I., Fallon J.T., Breslow J.L., Fisher E.A. Elevating high-density lipoprotein cholesterol in apolipoprotein E - deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content. Circulation, 2001, 104, 2447–2452 http://dx.doi.org/10.1161/hc4501.098952[Crossref]
• [20] Chereshnev I., Trogan E., Omerhodzic S., Itskovich V., Aguinaldo J.G., Fayad Z.A., Fisher E.A., Reis E.D. Mouse model of heterotopic aortic arch transplantation. J. Surg. Res., 2003, 111, 171–176 http://dx.doi.org/10.1016/S0022-4804(03)00039-8[Crossref]
• [21] Trogan E., Fayad Z.A., Itskovich V.V., Aguinaldo J.G., Mani V., Fallon J.T., Chereshnev I., Fisher E.A. Serial studies of mouse atherosclerosis by in vivo magnetic resonance imaging detect lesion regression after correction of dyslipidemia. Arterioscler. Thromb. Vasc. Biol., 2004, 24, 1714–1719 http://dx.doi.org/10.1161/01.ATV.0000139313.69015.1c[Crossref]
• [22] Hansson G.K. Immune mechanisms in atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2001, 21, 1876–1890 http://dx.doi.org/10.1161/hq1201.100220[Crossref]
• [23] Libby P. Inflammation in atherosclerosis. Nature, 2002, 420, 868–874 http://dx.doi.org/10.1038/nature01323[Crossref]
• [24] Boyle J.J. Macrophage activation in atherosclerosis: Pathogenesis and pharmacology of plaque rupture. Curr. Vasc. Pharmacol., 2005, 3, 63–68 http://dx.doi.org/10.2174/1570161052773861[Crossref]
• [25] Moos M.P.W., John N., Gräbner R., Nossmann S., Gunther B., Vollandt R., Funk C.D., Kaiser B., Habenicht A.J. The lamina adventitia is the major site of immune cell accumulation in standard chowfed apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 2386–2391 http://dx.doi.org/10.1161/01.ATV.0000187470.31662.fe[Crossref]
• [26] Tonar Z., Bobkova D., Havlickova J., Poledne R. Vessel transplantation of apolipoprotein E-deficient mice as a model of atherosclerosis regression. Atherosclerosis Suppl., 2005, 6, 45–45 http://dx.doi.org/10.1016/S1567-5688(05)80180-1[Crossref]
• [27] European Communities. European convention for the protection of vertebrate animals used for experimental and other scientific purposes. 1986, European Treaty Series No. 123, Strasbourg
• [28] Koulack J., McAlister V.C., Giacomantonio C.A., Bitter-Suermann H, MacDonald A.S., Lee T.D. Development of a mouse aortic transplant model of chronic rejection. Microsurgery, 1995, 16, 110–113 http://dx.doi.org/10.1002/micr.1920160213[Crossref]
• [29] Kocova J. Overall staining of connective tissue and the muscular layer of vessels. Fol. Morphol., 1970, 3, 293–295
• [30] Stary H.C. Natural History and Histological Classification of Atherosclerotic Lesions. An Update. Arterioscler. Thromb. Vasc. Biol., 2000, 20,, 1177–1178 [Crossref]
• [31] Nachtigal P., Semecky V., Kopecky M., Gojova A., Solichova D., Zdansky P., Zadak Z. Application of stereological methods for the quantification of VCAM-1and ICAM-1 expression in early stages of rabbit atherosclerosis. Pathol. Res. Pract., 2004, 200, 219–229 http://dx.doi.org/10.1016/j.prp.2004.02.008[Crossref]
• [32] Howard C.V., Reed M.G. Unbiased Stereology: Three Dimensional Measurement in Microscopy. 1st edn. Royal Microscopical Society and Springer-Verlag, New York, 1998.
• [33] Russ J.C., Dehoff R.T. Classical stereological measures. In: Russ J.C., Dehoff R.T. (Eds). Practical Stereology. 2nd edn. Plenum Press, New York, 2001
• [34] Gundersen H.J.G., Jensen E.B. The efficiency of systematic sampling in stereology and its prediction. J. Microsc., 1987, 147, 229–263
• [35] Stoyan D., Kendall W.S., Mecke J. Fibre and surface processes. In: Stoyan, D, Kendall, WS, Mecke, J (Eds). Stochastic geometry and its applications. 2nd edn. John Wiley & Sons, Chichester, 1996
• [36] Philimonenko A.A., Janacek J., Hozak P. Statistical evaluation of colocalisation patterns in immunogold labelling experiments. J. Struct. Biol., 2000, 132, 201–210 http://dx.doi.org/10.1006/jsbi.2000.4326[Crossref]
• [37] Shrout P.E., Fleiss J.L. Intraclass Correlations: Uses in Assessing Rater Reliability. Psych. Bull., 1979, 2, 420–428 http://dx.doi.org/10.1037/0033-2909.86.2.420[Crossref]
• [38] Lee P.C., Wang Z.L., Qian S., Watkins S.C., Lizonova A., Kovesdi I., Tzeng E., Simmons R.L., Billiar T.R., Shears L.L. Endothelial nitric oxide synthase protects aortic allografts from the development of transplant arteriosclerosis. Transplantation, 2000, 69, 1186–1192 http://dx.doi.org/10.1097/00007890-200003270-00025[Crossref]
• [39] Soleimani B., Shi V.C. Experimental models of graft arteriosclerosis. Methods Mol. Biol., 2006, 333, 401–424
• [40] Calfa M., Aitouche A., Vazquez-Padron R.I., Gay-Rabinstein C., Lasko D., Badell J., Farji A., El-Haddad A., Liotta C., Louis L.B., Simmonds A., Pestana I.A., Pang M., Li S., Pham S.M. Aging and transplant arteriosclerosis in absence of alloreactivity and immunosuppressive drugs in a rat aortic model: recipient age’s contribution. Transplantation, 2005, 79, 1683–1690 http://dx.doi.org/10.1097/01.TP.0000163467.93783.C8[Crossref]
• [41] Rauscher F.M., Goldschmidt-Clermont P.J., Davis B.H., Wang T., Gregg D., Ramaswami P., Pippen A.M., Annex B.H., Dong C., Taylor D.A. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation, 2003, 29, 457–463 http://dx.doi.org/10.1161/01.CIR.0000082924.75945.48[Crossref]
• [42] Chow L.H., Huh S., Jiang J., Zhong R., Pickering J.G. Intimal thickening develops without humoral immunity in a mouse aortic allograft model of chronic vascular rejection. Circulation, 1996, 94, 3079–3082 [Crossref]
• [43] Sun H., Valdivia L.A., Subbotin V. Improved surgical technique for the establishment of a murine model of aortic transplantation. Microsurgery, 1998, 18, 368–371 http://dx.doi.org/10.1002/(SICI)1098-2752(1998)18:6<368::AID-MICR5>3.0.CO;2-F[Crossref]
• [44] Hu Y., Davison F., Zhang Z., Xu Q. Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells. Circulation, 2003, 108, 3122–3127 http://dx.doi.org/10.1161/01.CIR.0000105722.96112.67[Crossref]
• [45] Sakihama H., Masunaga T., Yamashita K., Hashimoto T., Inobe M., Todo S., Uede T. Stromal cell-derived factor-1 and CXCR4 interaction is critical for development of transplant arteriosclerosis. Circulation, 2004, 110, 2924–2930 http://dx.doi.org/10.1161/01.CIR.0000146890.93172.6C[Crossref]
• [46] Gough P.J., Gomez I.G., Wille P.T., Raines E.W. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. Journal Clin. Invest., 2006, 116, 59–69 http://dx.doi.org/10.1172/JCI25074[Crossref]
• [47] Ensminger S.M., Spriewald B.M., Witzke O., Morrison K., Pajaro O.E., Morris P.J., Rose M.L., Wood K.J. Kinetics of transplant arteriosclerosis in MHC-class I mismatched and fully allogeneic mouse aortic allografts, Transplantation, 2002, 73, 1068–1074 http://dx.doi.org/10.1097/00007890-200204150-00009[Crossref]

Identifiers

DOI

10.2478/s11536-010-0006-9