Cardiovascular Pathology
Volume 20, Issue 4 , Pages 195-203, July 2011

iNOS induction and PARP-1 activation in human atherosclerotic lesions: an immunohistochemical and ultrastructural approach

  • Ida Perrotta

      Affiliations

    • Department of Ecology, University of Calabria, Rende, Cosenza, Italy
    • Corresponding Author InformationCorresponding author. Department of Ecology, University of Calabria, Arcavacata di Rende (Cosenza) 87036, Italy. Tel.: +39 0984 492976, +39 3471734173; fax: +39 0984 492986.
  • ,
  • Elvira Brunelli

      Affiliations

    • Department of Ecology, University of Calabria, Rende, Cosenza, Italy
  • ,
  • Alfonso Sciangula

      Affiliations

    • Department of Cardiothoracic Surgery and Cardiology, Sant'Anna Hospital, Catanzaro, Italy
  • ,
  • Francesco Conforti

      Affiliations

    • Department of Pathology, School of Medicine, University Magna Graecia, Catanzaro, Italy
  • ,
  • Enrico Perrotta

      Affiliations

    • Department of Ecology, University of Calabria, Rende, Cosenza, Italy
  • ,
  • Sandro Tripepi

      Affiliations

    • Department of Ecology, University of Calabria, Rende, Cosenza, Italy
  • ,
  • Giuseppe Donato

      Affiliations

    • Department of Pathology, School of Medicine, University Magna Graecia, Catanzaro, Italy
  • ,
  • Mauro Cassese

      Affiliations

    • Department of Cardiothoracic Surgery and Cardiology, Sant'Anna Hospital, Catanzaro, Italy

Received 7 August 2009; received in revised form 2 October 2009; accepted 2 June 2010. published online 09 July 2010.

Abstract 

Background

Several lines of clinical and experimental evidence have demonstrated that reactive oxygen species and nitrogen species are generated in unregulated amounts during diverse cardiovascular disorders. It has been previously reported by our group and others that augmented expression of nitric oxide synthase isoforms is associated with human atherogenesis and that the activity of the enzymes in an atherosclerotic environment may promote the formation of peroxynitrite. Among the downstream mechanisms triggered by oxidants, poly(ADP-ribose) polymerase-1 activation has recently been implicated in the pathogenesis of acute and chronic myocardial dysfunction, diabetes, hypertension, aging, and various forms of shock.

Methods

Based on these observations, we performed immunohistochemical and immunogold labeling analyses to evaluate the expression profile and the subcellular localization of inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 in healthy and atherosclerotic human aortae.

Results

We have demonstrated that inducible nitric oxide synthase colocalizes with poly(ADP-ribose) polymerase-1 within vascular cells of atherosclerotic human aortae. We have reported for the first time, to our knowledge, the ultrastructural localization of poly(ADP-ribose) polymerase-1 within the nuclei of lesional smooth muscle cells. Finally, we have evidenced that poly(ADP-ribose) polymerase-1 induction within cells of the diseased aorta strongly correlates with alterations in mitochondrial morphology.

Conclusions

Our data imply the possibility of a significant role for cross-talk between inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 in human atherosclerotic lesions. We conclude that the prooxidant milieu of the plaque might exert damaging effects on mitochondria via a poly(ADP-ribose) polymerase-1-mediated mechanism since the absence of the enzyme results in a corresponding lack of changes in mitochondrial morphology. The present report may open avenues for further researches that could have important therapeutic consequences for the treatment of atherosclerosis and its clinical sequelae.

Keywords: Atherosclerosis, iNOS, PARP-1, Oxidative stress, Mitochondrial damage

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 Financial support: The authors declare that no funding was available for this work.

PII: S1054-8807(10)00074-8

doi:10.1016/j.carpath.2010.06.002

Cardiovascular Pathology
Volume 20, Issue 4 , Pages 195-203, July 2011