title: iNOS induction and PARP-1 activation in human atherosclerotic lesions: an immunohistochemical and ultrastructural approach.
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.
authors.affiliation: Department of Ecology, University of Calabria, Rende, Cosenza, Italy. idaperrotta@yahoo.it
authors.forename: Ida
authors.initials: I
authors.lastname: Perrotta
authors.forename: Elvira
authors.initials: E
authors.lastname: Brunelli
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sciangula
authors.forename: Francesco
authors.initials: F
authors.lastname: Conforti
authors.forename: Enrico
authors.initials: E
authors.lastname: Perrotta
authors.forename: Sandro
authors.initials: S
authors.lastname: Tripepi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Donato
authors.forename: Mauro
authors.initials: M
authors.lastname: Cassese
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000378:metabolism / Q000648:ultrastructure; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases