Chronological changes of aortic and hepatic lesions in apolipoprotein E deficient mice

OTERO-LOSADA, MATILDE; MC LAUGHLIN SANTIAGO; G RODRIGUEZ GRANILLO; A MÜLLER; G OTTAVIANO; J MILEI

Artery Research

Elsevier

Año: 2011 p. 109 - 111

1872-9312

Conclusion High variability of plaque area and liver parenchymal inflammation found around 20 weeks could not be explained by time and exceeded interindividual variability observed at any other time. An evolving period characterized by rapid changes might alternatively explain high variability in plaque area and parenchymal inflammation observed at this time. The estimated half-time for severe lesions development as predicted by a sigmoidal data fitting equation (w20.4 weeks) is in agreement with previous reports showing full development of lesions around 40 weeks.8 A complex interplay of adhesive cellular interactions, chemotactic factors, proinflammatory chemokines and growth-regulatory molecules participates in atherogenesis. 9 Knowledge of the temporal course of putative atherosclerosis-related inflammation mediators across lifespan might help to identify key candidates responsible for atherosclerosis evolution in this mouse model. Atherosclerotic evolution might be associated with the progression to a severe inflammatory form of liver damage in apolipoprotein E-deficient mice. Present findings may suggest that a series of rapid and transient changes might take place around 20 weeks of life. These might be critical in determining the progression of tissue damage in this mouse model of atherosclerosis. References 1. Meir KS, Leitersdorf E. Atherosclerosis in the apolipoprotein-Edeficient mouse: a decade of progress. Arterioscler Thromb Vasc Biol 2004;24:1006e14. 2. Yin M, Zhang L, Sun XM, Mao LF, Pan J. Lack of apoE causes alteration of cytokines expression in young mice liver. Mol Biol Rep 2010;37:2049e54. 3. Bonomini F, Filippini F, Hayek T, Aviram M, Keidar S, Rodella LF, et al. ]polipoprotein E and its role in aging and survival. Exp Gerontol 2010;45:149e57. 4. Ferre´ N, Martı´nez-Clemente M, Lo´pez-Parra M, Gonza´lez- Pe´riz A, Horrillo R, Planaguma` A, et al. Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols. Am J Physiol Gastrointest Liver Physiol 2009;296:G553e562. 5. Martı´nez-Clemente M, Ferre´ N, Gonza´lez-Pe´riz A, Lo´pez- Parra M, Horrillo R, Titos E, et al. 5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alphainduced hepatocyte damage in hyperlipidemia-prone ApoE-null mice. Hepatology 2010;51:817e27. 6. Alkhouri N, Tamimi TA, Yerian L, Lopez R, Zein NN, Feldstein AE.The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Dig Dis Sci 2010;55:2644e50. 7. Collier J. Non-alcoholic fatty liver disease. Medicine 2007;35: 86e8. 8. Martin G, Dol F, Mare´s AM, Berezowski V, Staels B, Hum DW, et al. Lesion progression in apoE-deficient mice: implication of chemokines and effect of the AT1 angiotensin II receptor antagonist ibesartan. J Cardiovasc Pharmacol 2004;43:191e9. 9. Mach Francois. The role of chemokines in atherosclerosis. Curr Atheroscler Rep 2001;3:243e51