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

doi:10.1016/j.jacbts.2017.10.002

Nitrosative Stress as a Modulator of Inflammatory Change in a Model of Takotsubo Syndrome

JACC Basic Transl Sci. 2018 Apr 18;3(2):213-226. doi: 10.1016/j.jacbts.2017.10.002. eCollection 2018 Apr.

Authors

Sven Y Surikow^{1

2}, Thanh H Nguyen^{1

2}, Irene Stafford¹, Matthew Chapman¹, Sujith Chacko¹, Kuljit Singh^{1

2}, Giovanni Licari², Betty Raman^{1

2}, Darren J Kelly³, Yuan Zhang³, Mark T Waddingham³, Doan T Ngo¹, Alexander P Bate¹, Su Jen Chua¹, Michael P Frenneaux⁴, John D Horowitz^{1

2}

Affiliations

¹ The Queen Elizabeth Hospital, Department of Cardiology, University of Adelaide, South Australia, Australia.
² Basil Hetzel Institute, Adelaide, South Australia, Australia.
³ Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Australia.
⁴ University of East Anglia, Norfolk, United Kingdom.

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.

Keywords: 3AB, 3-aminobenzamide; ANOVA, analysis of variance; ISO, isoproterenol; LV, left ventricular; NFκB, nuclear factor kappa B; NO, nitric oxide; NOS, nitric oxide synthase; NT, nitrotyrosine; O2–, superoxide; ONOO–, peroxynitrite; PAR, poly(ADP-ribose); PARP, poly(ADP-ribose) polymerase; TS, Takotsubo syndrome; TXNIP, thioredoxin-interacting protein; Takotsubo cardiomyopathy; myocardial inflammation; oxidative stress; poly(ADP-ribose) polymerase-1.