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Attenuation of Neointima Formation Following Arterial Injury in PAI-1 Deficient Mice

Authors

  • VICTORIA A. PLOPLIS,

    Corresponding author
    1. W.M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
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  • FRANCIS J. CASTELLINO

    1. W.M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
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Address for correspondence: Victoria A. Ploplis, Department of Chemistry and Biochemistry, Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA. Voice: 219-631-4017; fax: 219-631-4048; ploplis.3@nd.edu.

Abstract

Abstract: Atherosclerosis is a chronic inflammatory disease in which the fibrinolytic system has been implicated as playing a major role. In order to directly assess the physiological impact an imbalanced fibrinolytic system has on both early and late stages of this disease, mice deficient for PAI-1 (PAI-1−/−) were used in a model of vascular injury/repair and compared to wildtype mice (WT). Copper-containing cuffs were placed around the carotid arteries of these mice and the injured arteries were removed at either 7 or 21 days for histological analyses. At both times after injury, fibrin was prevalent in WT arteries, whereas only diffuse in PAI-1−/− arteries. At 21 days after injury, a prominent, multilayered neointima was evident in WT arteries, with no evidence of a neointima in PAI-1−/− arteries. Results from this study directly confirm the involvement of the fibrinolytic system in vascular repair processes following injury and indicate that fibrin could potentially play a role in lesion formation by stimulating smooth muscle cell proliferation, collagen synthesis, and intracellular cholesterol accumulation.

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