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The C57Bl/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl/6N

  • Markus Wortmann
    Correspondence
    Corresponding author. Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Muhammad Arshad
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Andreas S. Peters
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Author Footnotes
    1 Present address. Luzerner Kantonsspital, Department of Vascular Surgery, Spitalstrasse, 6000 Luzern 16, Switzerland.
    Maani Hakimi
    Footnotes
    1 Present address. Luzerner Kantonsspital, Department of Vascular Surgery, Spitalstrasse, 6000 Luzern 16, Switzerland.
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Dittmar Böckler
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Susanne Dihlmann
    Affiliations
    University Hospital Heidelberg, Department of Vascular and Endovascular Surgery, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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  • Author Footnotes
    1 Present address. Luzerner Kantonsspital, Department of Vascular Surgery, Spitalstrasse, 6000 Luzern 16, Switzerland.

      Highlights

      • C57BL/6J and 6N mice present several phenotypic differences with relevance to cardiovascular research.
      • C57BL/6J mice are more susceptible to formation of aneurysms than C57Bl/6N mice.
      • C57Bl/6J aortic smooth muscle cells have a more synthetic and inflammatory phenotype.
      • C57Bl/6J smooth muscle cells present higher levels of NADP/NADPH and oxidative DNA modifications.

      Abstract

      Background and aims

      Genetic variations between C57Bl/6 mouse substrains are highly relevant to the investigation of cardiovascular disease. We here assessed whether these variations have an impact on the incidence of abdominal aortic aneurysms (AAA) in C57Bl/6J and 6 N mice.

      Methods

      AAA were induced by subcutaneous infusion of 1500 ng/kg*min Angiotensin-II for four weeks in six-month-old male CB57Bl/6J and 6N mice. Aortic smooth muscle cells (VSMC) were isolated from untreated animals for in vitro analysis.

      Results

      C57Bl/6J mice are more susceptible to AAA formation (76.5% vs. 7.1%, p = 0.0002). C57Bl/6J VSMC expressed more pro-inflammatory molecules such as Nlrp3, Aim2 and NF-κB. Additionally, these cells presented significantly higher levels of NADP/NADPH and oxidative DNA modifications, as indicated by 8-OHdG-staining, compared to C57Bl/6N VSMC.

      Conclusions

      In contrast to previous reports, we present evidence that six-month-old C57BL/6J, but not C57BL/6N mice develop AAA. In accordance with the deficiency of nicotinamide-nucleotide-transhydrogenase (Nnt), C57BL/6J VSMC displayed increased oxidative stress, oxidative DNA damage and a stronger inflammatory phenotype than C57BL/6N VSMC.

      Graphical abstract

      Keywords

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