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
JACC-BASIC TO TRANSLATIONAL SCIENCE | ELSEVIER SCIENCE INC | Published : 2018
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..View full abstract
This work was funded in part by a Project Grant fromthe National Health and Medical Research Council (Australia). Mr. Surikow, Dr. Raman, and Dr. Singh were recipients of Postgraduate Research Scholarships from the University of Adelaide (Mr. Surikow and Dr. Singh) and fromthe Cardiac Society of Australia and New Zealand (Dr. Raman). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.