Effect of acetylsalicylic acid on nuclear factor-κB activation and on late preconditioning against infarction in the myocardium

Gabor Jancso, Barbara Cserepes, Balázs Gasz, Laszlo Benko, Andrea Ferencz, Balazs Borsiczky, Janos Lantos, Anjali Dureja, Katalin Kiss, Jozsef Szeberényi, Elizabeth Roth

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22 Citations (Scopus)

Abstract

Nuclear factor-κB (NF-κB) plays an essential role in the intracellular signal transduction of the second window of protection (SWOP). Acetylsalicylic acid (ASA) blocks NF-κB-dependent gene activation in leukocytes and endothelial cells through preventing phosphorylation and subsequent degradation of the inhibitor IκB-α. This study investigated the effect of ASA on the late phase of ischemic preconditioning (PC) against myocardial infarction and on the activation of NF-κB in the preconditioned myocardium. Conscious rabbits were subjected to 4 cycles of 5 minutes of coronary occlusion and 5 minutes of reperfusion together with 3 different doses of ASA (5 mg/kg; 25 mg/kg; 130 mg/kg). After 30 minutes of reperfusion we determined the activation of NF-κB with an electrophoretic mobility shift assay (EMSA). Twenty-four hours later, after 30 minutes of test ischemia, we performed infarct size analysis using triphenyltetrazolium-chloride (TTC) staining. Neither 5 mg/kg (antithrombotic dose) nor 25 mg/kg (analgesic/antipyretic dose) of ASA interfered with the NF-κB activation and the protective effect of late preconditioning against myocardial infarction. In contrast, NF-κB activation and late PC effect were completely abrogated by 130 mg/kg of ASA. Our results suggest that nonselective doses of NSAIDs should be used with caution in patients with atherosclerotic cardiovascular disease because they may deprive the heart of its innate defensive response.

Original languageEnglish
Pages (from-to)295-301
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume46
Issue number3
DOIs
Publication statusPublished - szept. 1 2005

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ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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