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Overexpression of copper/zinc superoxide dismutase in the median preoptic nucleus improves cardiac function after myocardial infarction in the rat
Author(s) -
Collister John P,
Hartnett Cristina,
Mayerhofer Tim,
Nahey David,
Stauthammer Christopher,
Krüger Maxie,
Tobias Anthony,
O'Sullivan M. Gerard,
Parker Josh,
Tian Jun,
Case Adam J,
Zimmerman Matthew C
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12607
Subject(s) - superoxide dismutase , ventricle , medicine , cardiac function curve , endocrinology , pathophysiology , myocardial infarction , chemistry , heart failure , dismutase , ejection fraction , oxidative stress
Summary Previous reports indicate that overexpression of copper/zinc superoxide dismutase (CuZn SOD ), an intracellular superoxide (O 2 •− ) scavenging enzyme, in the brain subfornical organ improves cardiac function in a mouse model of heart failure ( HF ). A downstream hypothalamic site, the Mn PO , may act as a relay centre for O 2 •− to serve as a mediator in the pathophysiology of HF . To test the hypothesis that elevated O 2 •− in the Mn PO contributes to the pathophysiology of HF and decreased cardiac function, we injected adenovirus encoding CuZn SOD (AdCuZn SOD , n=7) or control empty adenovirus vector (AdEmpty, n=7) into the Mn PO 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 CuZn SOD expression in Mn PO via immunofluorescence and histopathological analyses of cardiac infarct size were conducted. Baseline ( EF ) ejection fractions (%) of AdCuZn SOD and AdEmpty rats were 73 ± 1 and 71 ± 1, respectively. Two weeks after MI , EF was significantly decreased in both groups of rats (AdCuZn SOD : 51 ± 3, AdEmpty: 46 ± 1). In contrast, by 4 weeks post MI , EF had improved to 64 ± 2 in AdCuZn SOD rats, yet was only 52 ± 1 in AdEmpty rats, and this was accompanied by lower plasma noradrenaline levels in AdCuZn SOD 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 CuZn SOD in the Mn PO was related to an improvement in left ventricular function and concomitant decreased plasma noradrenaline levels 4 weeks post MI.