Nitrosative stress as a modulator of inflammatory change in a model of Takotsubo Syndrome

Sven Y. Surikow, Thanh H. Nguyen, Irene Stafford, Matthew Chapman, Sujith Chacko, Kuljit Singh, Giovanni Licari, Betty Raman, Darren J. Kelly, Yuan Zhang, Mark T. Waddingham, Doan T. Ngo, Alexander P. Bate, Su Jen Chua, Michael P. Frenneaux, John D. Horowitz

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Abstract

Previous studies have shown that patients with Takotsubo syndrome (TS) have supranormal nitric oxide signaling, and post-mortem studies of TS heart samples revealed nitrosative stress. Therefore, we first showed in a female rat model that isoproterenol induces TS-like echocardiographic changes, evidence of nitrosative stress, and consequent activation of the energy-depleting enzyme poly(ADP-ribose) polymerase-1. We subsequently showed that pre-treatment with an inhibitor of poly(ADP-ribose) polymerase-1 ameliorated contractile abnormalities. These findings thus add to previous reports of aberrant β-adrenoceptor signaling (coupled with nitric oxide synthase activation) to elucidate mechanisms of impaired cardiac function in TS and point to potential methods of treatment.
Original languageEnglish
Pages (from-to)213-226
Number of pages14
JournalJACC: Basic to Translational Science
Volume3
Issue number2
Early online date18 Apr 2018
DOIs
Publication statusPublished - Apr 2018

Keywords

  • Takotsubo cardiomyopathy
  • myocardial inflammation
  • oxidative stress
  • poly(ADP-Ribose) polymerase-1

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