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Psychosocial stress exacerbates disease outcome in mice with muscular dystrophy
Author(s) -
Sabharwal Rasna,
Poglitsch Marko,
Yang Liping,
Weiss Robert M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.859.7
Subject(s) - medicine , cardiomyopathy , muscular dystrophy , endocrinology , dilated cardiomyopathy , cardiology , angiotensin ii , sudden cardiac death , blood pressure , heart failure
Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and dilated cardiomyopathy (DCM). We have demonstrated that sarcoglycan delta deficient (Sgcd−/−) mice, an established model of muscular dystrophy, exhibit angiotensin II (Ang II)‐dependent autonomic dysfunction at a young age which worsens with aging, and predicts development of DCM [Exp Physiol 2015] . Patients afflicted with muscular dystrophy often exhibit symptoms of psychosocial stress such as cognitive impairment, depression, sadness, and anxiety. Several studies indicate that there is a bidirectional association between psychosocial stress and cardiac risk. Therefore, our goals were to determine whether (i) psychological stress and autonomic dysfunction synergistically confer susceptibility to cardiac arrhythmias and sudden death in Sgcd−/− mice; and (ii) activation of the cardiac renin angiotensin system (RAS) contributes to these catastrophic events in the Sgcd−/− mice. Blood pressure (BP), heart rate (HR), electrocardiogram and HR variability (HRV) were measured by telemetry in control C57BL/6J (n=6) and Sgcd−/− (n=8) middle‐aged mice (50–60 weeks of age). Cardiac RAS peptides were measured by mass spectrometry while Ang II type 1 receptor (AT 1 R) expression was quantified by immunofluorescence. Exposure to acute mild psychosocial stress (~15 min exposure to intruder mouse) transiently increased HR and decreased HRV, which was followed by progressive bradyarrhythmias, hypotension, and death in 40% of Sgcd−/− mice (all P<0.05 vs. C57BL/6J). Interestingly, Sgcd−/− mice exhibited profound increases in plasma corticosterone (+86%) and cardiac Ang II (+67%), and AT 1 Rs (+72%), Masson); while level of the cardioprotective peptide Ang‐[1–7] was markedly decreased (−75%) (all P<0.05 vs. C57BL/6J). We conclude that middle‐aged Sgcd−/− mice exhibit activation of the cardiac RAS and are susceptible to stress‐induced cardiac arrhythmias and sudden death.