Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

Claudio Napoli, Eric Ackah, Filomena De Nigris, Piero Del Soldato, Francesco P. D'Armiento, Ettore Crimi, Marios Condorelli, William C. Sessa

Research output: Contribution to journalArticle

Abstract

The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 ± 12.3% compared with that of the placebo (P <0.001). Regular aspirin did not reduce significantly aortic lesions (-5.1 ± 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P <0.001) as well as by the prolongation of lag-time (P <0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX4016 (P <0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P <0.01), and macrophages-derived foam cells (F4/80 monoclonal antibody, P <0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice.

Original languageEnglish
Pages (from-to)12467-12470
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number19
DOIs
Publication statusPublished - Sep 17 2002

Keywords

  • Atherosclerosis
  • LDL-receptor-deficient mice

ASJC Scopus subject areas

  • Genetics
  • General

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