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Myeloid related protein (MRP) 14 expressing monocytes infiltrate atherosclerotic lesions of ApoE null mice

      The consequences of atherosclerotic plaque formation result in a number of diseases of the cardiovascular system which represent a serious health problem and major cause of death in the western world. Despite a growing research interest the pathogenesis of atherosclerosis especially regarding the initial steps of the disease and the participation of immune cells is not fully understood yet. Since these investigations are hard to manage in humans the development of animal models which closely resemble human conditions has long been an important research goal. Mice deficient in production of apolipoprotein (Apo) E are a useful model since they develop advanced atherosclerotic lesions at several locations throughout the arterial tree which show the typical features of those in man: early fatty streak formation, later calcification and development of necrotic cores and fibrous caps [
      • Nakashima Y.
      • Plump A.S.
      • Reines E.W.
      • Breslow J.L.
      • Ross R.
      ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
      ,
      • Reddick R.L.
      • Zhang S.H.
      • Maeda N.
      Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.
      ,
      • Zhang S.H.
      • Reddick R.L.
      • Piedrahita J.A.
      • Maeda N.
      Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.
      ]. ApoE −/− mice were generated by gene targeting [
      • Plump A.S.
      • Smith J.D.
      • Hayek T.
      • et al.
      Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.
      ,
      • Piedrahita J.A.
      • Zhan S.H.
      • Hagaman J.R.
      • Oliver P.M.
      • Maeda N.
      Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embrionic stem cells.
      ,
      • Tsukamoto K.
      • Tangirala R.
      • Chun S.H.
      • Pure E.
      • Rader D.J.
      Rapid regression of atherosclerosis induced by liver-directed gene transfer of ApoE in ApoE-deficient mice.
      ] and develop advanced atherosclerotic lesions and hypercholesterolaemia under a normal chow diet at about 6–8 months age. This animal model is widely used in recent studies about the pathomechanisms of atherosclerosis [
      • Tsukamoto K.
      • Tangirala R.
      • Chun S.H.
      • Pure E.
      • Rader D.J.
      Rapid regression of atherosclerosis induced by liver-directed gene transfer of ApoE in ApoE-deficient mice.
      ,
      • Zhou X.
      • Hansson G.K.
      Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice.
      ,
      • Couffinhal T.
      • Silver M.
      • Kearney M.
      • et al.
      Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE−/− mice.
      ,
      • Ramos C.L.
      • Huo Y.
      • Jung U.
      • Ghosh S.
      • Manka D.R.
      • Sarembock I.J.
      • Ley K.
      Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell of vascular endothelial growth factor in ApoE−/− mice.
      ,
      • George J.
      • Gilburd B.
      • Levkovitz H.
      • et al.
      Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis.
      ,
      • Nakashima Y.
      • Raines E.W.
      • Plump A.S.
      • Breslow J.L.
      • Ross R.
      Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse.
      ,
      • Gupta S.
      • Pablo A.M.
      • Jiang Xc.
      • Wang N.
      • Tal I.
      IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.
      ,
      • Fazio S.
      • Babaev V.R.
      • Murray A.B.
      • et al.
      Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
      ].

      Keywords

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      References

        • Nakashima Y.
        • Plump A.S.
        • Reines E.W.
        • Breslow J.L.
        • Ross R.
        ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
        Arterioscler. Thromb. 1994; 14: 133-140
        • Reddick R.L.
        • Zhang S.H.
        • Maeda N.
        Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.
        Arterioscler. Thromb. 1994; 14: 141-147
        • Zhang S.H.
        • Reddick R.L.
        • Piedrahita J.A.
        • Maeda N.
        Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.
        Science. 1992; 258: 468-471
        • Plump A.S.
        • Smith J.D.
        • Hayek T.
        • et al.
        Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.
        Cell. 1992; 71: 343-353
        • Piedrahita J.A.
        • Zhan S.H.
        • Hagaman J.R.
        • Oliver P.M.
        • Maeda N.
        Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embrionic stem cells.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 4471-4475
        • Tsukamoto K.
        • Tangirala R.
        • Chun S.H.
        • Pure E.
        • Rader D.J.
        Rapid regression of atherosclerosis induced by liver-directed gene transfer of ApoE in ApoE-deficient mice.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 2162-2170
        • Zhou X.
        • Hansson G.K.
        Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice.
        Scand. J. Immunol. 1999; 50: 25-30
        • Couffinhal T.
        • Silver M.
        • Kearney M.
        • et al.
        Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE−/− mice.
        Circulation. 1999; 22: 3188-3198
        • Ramos C.L.
        • Huo Y.
        • Jung U.
        • Ghosh S.
        • Manka D.R.
        • Sarembock I.J.
        • Ley K.
        Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell of vascular endothelial growth factor in ApoE−/− mice.
        Circ. Res. 1999; 84: 1237-1244
        • George J.
        • Gilburd B.
        • Levkovitz H.
        • et al.
        Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis.
        Atherosclerosis. 1998; 138: 147-152
        • Nakashima Y.
        • Raines E.W.
        • Plump A.S.
        • Breslow J.L.
        • Ross R.
        Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse.
        Arterioscler. Thromb. Vasc. Biol. 1998; 18: 842-851
        • Gupta S.
        • Pablo A.M.
        • Jiang Xc.
        • Wang N.
        • Tal I.
        IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.
        J. Clin. Invest. 1997; 99: 2752-2761
        • Fazio S.
        • Babaev V.R.
        • Murray A.B.
        • et al.
        Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
        Proc. Natl. Acad. Sci. USA. 1997; 94: 4647-4652
        • Bobryshev Y.V.
        • Babaev V.R.
        • Iwasa S.
        • Lord R.S.A.
        • Watanabe T.
        Atherosclerotic lesions of apolipoprotein E deficient mice contain cells expressing S 100 protein.
        Athersosclerosis. 1999; 143: 451-454
        • Bobryshev Y.V.
        • Lord R.S.A.
        S-100 positive cells in human arterial intima and in atherosclerotic lesions.
        Cardiovasc. Res. 1995; 29: 689-696
        • Ozmen J.
        • Lord R.S.A.
        • Bobryshev Y.V.
        • Ashwell K.W.S.
        • Munro V.F.
        S 100 protein is expressed in induced atherosclerotic lesions of hypercholesterolaemic rats.
        Biomed. Res. 1998; 19: 279-287
        • Topoll H.
        • Zwadlo G.
        • Lange D.E.
        • Sorg C.
        Phenotypic dynamics of macrophage subpopulations during human experimental gingivitis.
        J. Peridontal Res. 1989; 24: 106-111
        • Roth J.
        • Sunderkötter C.
        • Goebler M.
        • Gutwald J.
        • Sorg C.
        Expression of the Ca2+ binding proteins MRP8 and MRP14 by early infiltrating cells in experimental contact dermatitis.
        Int. Arch. Allergy Immunol. 1992; 98: 140-148
        • Hogg N.
        • Allen C.
        • Edgeworth G.
        Monoclonal antibody 5.5 reacts with p8, 14, a myeloid molecule associated with some vascular endothelium.
        Eur. J. Immunol. 1989; 19: 1053-1060
        • Roth J.
        • Burwinkel F.
        • van den Bos C.
        • Goebler M.
        • Vollmer E.
        • Sorg C.
        MRP8 and MRP14, S-100-like proteins associated with myeloid differentiation, are translocated to plasma membrane and intermediate filaments in a calcium-dependent manner.
        Blood. 1993; 82: 1875-1881
        • Newton R.A.
        • Hogg N.
        The human S 100 Protein MRP14 is a Novel Activator of the β2 integrin Mac-1 on neutrophils.
        J. Immunol. 1998; 160: 1427-1434
        • Paigen B.
        • Morrow A.
        • Holmes P.A.
        • Mitchell D.
        • Williams R.A.
        Quantitative assessment of atherosclerotic lesions in mice.
        Atherosclerosis. 1987; 68: 231-240