Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice

Claudio Napoli, Giuseppe Cirino, Piero Del Soldato, Raffaella Sorrentino, Vincenzo Sica, Mario Condorelli, Aldo Pinto, Louis J. Ignarro

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Abstract

Restenosis is due to neointimal hyperplasia, which occurs in the coronary artery after percutaneous transluminal coronary angioplasty (PTCA). During restenosis, an impairment of nitric oxide (NO)-dependent pathways may occur. Concomitant hypercholesterolemia may exacerbate restenosis in patients undergoing PTCA. Here, we show that a NO-releasing aspirin derivative (NCX-4016) reduces the degree of restenosis after balloon angioplasty in low-density lipoprotein receptor-deficient mice and this effect is associated with reduced vascular smooth muscle cell (VSMC) proliferation and macrophage deposition at the site of injury. Drugs were administered following both therapeutic or preventive protocols. We demonstrate that NCX-4016 is effective both in prevention and treatment of restenosis in the presence of hypercholesterolemia. These data indicate that impairment of NO-dependent mechanisms may be involved in the development of restenosis in hypercholesterolemic mice. Although experimental models of restenosis may not reflect restenosis in humans in all details, we suggest that a NO-releasing aspirin derivative could be an effective drug in reducing restenosis following PTCA, especially in the presence of hypercholesterolemia and/or gastrointestinal damage.

Original languageEnglish
Pages (from-to)2860-2864
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number5
DOIs
Publication statusPublished - Feb 27 2001

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Aspirin
Coronary Balloon Angioplasty
Hypercholesterolemia
Nitric Oxide
Balloon Angioplasty
LDL Receptors
Vascular Smooth Muscle
Pharmaceutical Preparations
Smooth Muscle Myocytes
Hyperplasia
Coronary Vessels
Theoretical Models
Macrophages
Cell Proliferation
nitroaspirin
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

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Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice. / Napoli, Claudio; Cirino, Giuseppe; Del Soldato, Piero; Sorrentino, Raffaella; Sica, Vincenzo; Condorelli, Mario; Pinto, Aldo; Ignarro, Louis J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 5, 27.02.2001, p. 2860-2864.

Research output: Contribution to journalArticle

Napoli, Claudio ; Cirino, Giuseppe ; Del Soldato, Piero ; Sorrentino, Raffaella ; Sica, Vincenzo ; Condorelli, Mario ; Pinto, Aldo ; Ignarro, Louis J. / Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 5. pp. 2860-2864.
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