TY - JOUR
T1 - Overexpression of copper/zinc superoxide dismutase in the median preoptic nucleus improves cardiac function after myocardial infarction in the rat
AU - Collister, John P.
AU - Hartnett, Cristina
AU - Mayerhofer, Tim
AU - Nahey, David
AU - Stauthammer, Christopher
AU - Krüger, Maxie
AU - Tobias, Anthony
AU - O'Sullivan, M. Gerard
AU - Parker, Josh
AU - Tian, Jun
AU - Case, Adam J.
AU - Zimmerman, Matthew C.
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Australia, Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Previous reports indicate that overexpression of copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2 •−) scavenging enzyme, in the brain subfornical organ improves cardiac function in a mouse model of heart failure (HF). A downstream hypothalamic site, the MnPO, may act as a relay centre for O2 •− to serve as a mediator in the pathophysiology of HF. To test the hypothesis that elevated O2 •− in the MnPO contributes to the pathophysiology of HF and decreased cardiac function, we injected adenovirus encoding CuZnSOD (AdCuZnSOD, n=7) or control empty adenovirus vector (AdEmpty, n=7) into the MnPO of normal rats. Subsequently, rats were subjected to coronary artery ligation to create a myocardial infarct (MI) of the left ventricle. Cardiac function was monitored via echocardiography. Upon completion, rat brains were examined for CuZnSOD expression in MnPO via immunofluorescence and histopathological analyses of cardiac infarct size were conducted. Baseline (EF) ejection fractions (%) of AdCuZnSOD and AdEmpty rats were 73 ± 1 and 71 ± 1, respectively. Two weeks after MI, EF was significantly decreased in both groups of rats (AdCuZnSOD: 51 ± 3, AdEmpty: 46 ± 1). In contrast, by 4 weeks post MI, EF had improved to 64 ± 2 in AdCuZnSOD rats, yet was only 52 ± 1 in AdEmpty rats, and this was accompanied by lower plasma noradrenaline levels in AdCuZnSOD rats (0.49 ± 0.19 ng/mL) compared to AdEmpty rats (1.20 ± 0.32 ng/mL). In conclusion, despite decreases in EF early after MI, overexpression of CuZnSOD in the MnPO was related to an improvement in left ventricular function and concomitant decreased plasma noradrenaline levels 4 weeks post MI.
AB - Previous reports indicate that overexpression of copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2 •−) scavenging enzyme, in the brain subfornical organ improves cardiac function in a mouse model of heart failure (HF). A downstream hypothalamic site, the MnPO, may act as a relay centre for O2 •− to serve as a mediator in the pathophysiology of HF. To test the hypothesis that elevated O2 •− in the MnPO contributes to the pathophysiology of HF and decreased cardiac function, we injected adenovirus encoding CuZnSOD (AdCuZnSOD, n=7) or control empty adenovirus vector (AdEmpty, n=7) into the MnPO of normal rats. Subsequently, rats were subjected to coronary artery ligation to create a myocardial infarct (MI) of the left ventricle. Cardiac function was monitored via echocardiography. Upon completion, rat brains were examined for CuZnSOD expression in MnPO via immunofluorescence and histopathological analyses of cardiac infarct size were conducted. Baseline (EF) ejection fractions (%) of AdCuZnSOD and AdEmpty rats were 73 ± 1 and 71 ± 1, respectively. Two weeks after MI, EF was significantly decreased in both groups of rats (AdCuZnSOD: 51 ± 3, AdEmpty: 46 ± 1). In contrast, by 4 weeks post MI, EF had improved to 64 ± 2 in AdCuZnSOD rats, yet was only 52 ± 1 in AdEmpty rats, and this was accompanied by lower plasma noradrenaline levels in AdCuZnSOD rats (0.49 ± 0.19 ng/mL) compared to AdEmpty rats (1.20 ± 0.32 ng/mL). In conclusion, despite decreases in EF early after MI, overexpression of CuZnSOD in the MnPO was related to an improvement in left ventricular function and concomitant decreased plasma noradrenaline levels 4 weeks post MI.
KW - heart failure
KW - median preoptic nucleus
KW - myocardial infarction
KW - noradrenaline
KW - superoxide dismutase
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U2 - 10.1111/1440-1681.12607
DO - 10.1111/1440-1681.12607
M3 - Article
C2 - 27297082
AN - SCOPUS:84984996442
SN - 0305-1870
VL - 43
SP - 960
EP - 966
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 10
ER -