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Vascular remodeling in ApoE-deficient mice: Diet dependent modulation after carotid ligation

  • Author Footnotes
    1 These authors contributed equally to this paper and should be considered first authors.
    H. Eschert
    Footnotes
    1 These authors contributed equally to this paper and should be considered first authors.
    Affiliations
    Leibniz-Institute for Arteriosclerosis Research, Münster, Germany

    Department of Cardiology and Angiology, Hospital of the University of Münster, Germany

    Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Germany
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this paper and should be considered first authors.
    J.R. Sindermann
    Footnotes
    1 These authors contributed equally to this paper and should be considered first authors.
    Affiliations
    Leibniz-Institute for Arteriosclerosis Research, Münster, Germany

    Department of Cardiology and Angiology, Hospital of the University of Münster, Germany

    Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Germany
    Search for articles by this author
  • H.H. Scheld
    Affiliations
    Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Germany
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  • G. Breithardt
    Affiliations
    Leibniz-Institute for Arteriosclerosis Research, Münster, Germany

    Department of Cardiology and Angiology, Hospital of the University of Münster, Germany
    Search for articles by this author
  • G. Weissen-Plenz
    Correspondence
    Corresponding author at: Leibniz-Institute for Arteriosclerosis Research, Domagkstr. 3, D-48149 Münster, Germany. Tel.: +49 251 835 6425; fax: +49 251 835 2998.
    Affiliations
    Leibniz-Institute for Arteriosclerosis Research, Münster, Germany

    Department of Cardiology and Angiology, Hospital of the University of Münster, Germany

    Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Germany
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this paper and should be considered first authors.

      Abstract

      Vascular remodeling is influenced by trauma and proatherogenic factors such as cholesterol. It has been shown that cholesterol exerts a direct effect on vessel wall structure. In this study we evaluated the effects of vascular trauma and cholesterol treatment on vascular remodeling and plaque integrity in carotid ligated ApoE-deficient mice.
      The right carotid artery was ligated in mice fed regular chow or cholesterol and fat containing diet. After 4 weeks left (non-ligated) and right (ligated) carotids were prepared. For studying vascular remodeling the vascular areas were evaluated morphometrically by calculating the areas from circumference measurements on Verhoff-van Gieson stains. The cellular and structural features of the plaque were analyzed by histological staining and immunohistochemistry.
      Under regular chow total vessel area decreased by 35% (p < 0.001); cholesterol-rich diet led to an increase by 20% (p < 0.05). In both feeding groups ligated carotids presented neointima development. The medial area increased only in mice fed regular chow. The luminal area was reduced by 80% (regular chow: p < 0.001) and by 90% (cholesterol-rich diet: p < 0.01). Regular chow led to structured plaques showing the typical features of stable plaques. Under cholesterol diet well defined plaque structures were missing. These lesions were characterized by numerous macrophages, few mostly PCNA positive smooth muscle cell (SMC) and less collagen particularly in the shoulder region.
      Our data indicate that in ApoE-deficient mice both direction of the remodeling response and lesion integrity are due to the diet applied: regular chow led to constrictive remodeling, whereas cholesterol and fat containing diet was associated with an adaptive response. Our data further indicate that the direction of response is not only related to the macrophage content but also to a proliferative intimal SMC-phenotype. Our data implicate that high serum cholesterol levels are not only inducers of plaque instability but also of the so far “positively recorded” compensatory remodeling.

      Keywords

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