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

Autor: Irene Stafford, Sujith Chacko, B. Raman, Matthew Chapman, Giovanni Licari, John D. Horowitz, Michael P. Frenneaux, Sven Y. Surikow, Thanh H Nguyen, Doan T.M. Ngo, S. Chua, Yuan Zhang, Darren J. Kelly, Mark T. Waddingham, Alexander P. Bate, Kuljit Singh
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Cardiac function curve
ISO
isoproterenol
medicine.medical_specialty
lcsh:Diseases of the circulatory (Cardiovascular) system
PARP
poly(ADP-ribose) polymerase
3AB
3-aminobenzamide
Poly ADP ribose polymerase
poly(ADP-ribose) polymerase-1
030204 cardiovascular system & hematology
medicine.disease_cause
Nitric oxide
PRECLINICAL RESEARCH
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
oxidative stress
O2–
superoxide
NOS
nitric oxide synthase
LV
left ventricular
ANOVA
analysis of variance
TS
Takotsubo syndrome
NT
nitrotyrosine
myocardial inflammation
NO
nitric oxide
biology
Nitrotyrosine
TXNIP
thioredoxin-interacting protein
Nitric oxide synthase
030104 developmental biology
Endocrinology
chemistry
3-Aminobenzamide
lcsh:RC666-701
NFκB
nuclear factor kappa B
biology.protein
Takotsubo cardiomyopathy
PAR
poly(ADP-ribose)
ONOO–
peroxynitrite
Cardiology and Cardiovascular Medicine
Oxidative stress
Peroxynitrite
Zdroj: JACC: Basic to Translational Science, Vol 3, Iss 2, Pp 213-226 (2018)
JACC: Basic to Translational Science
Popis: Visual Abstract
Highlights • Treatment of female rats with a single dose of isoproterenol results in apical hypokinesis mimicking Takotsubo syndrome • Myocardial inflammation includes increased content of 3-nitrotyrosine and poly(ADP-ribose), indicating nitrosative stress and PARP-1 activation, respectively • Pretreatment with 3-aminobenzamide (a PARP-1 inhibitor) attenuates negative inotropic changes • We conclude that the peroxynitrite/PARP-1 cascade contributed to negative inotropy in this model of Takotsubo syndrome, consistent with the limited data available in patients
Summary 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.
Databáze: OpenAIRE
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