Overexpression of copper/zinc superoxide dismutase in the median preoptic nucleus improves cardiac function after myocardial infarction in the rat.
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.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
John P
JP
Collister
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Cristina
C
Hartnett
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Tim
T
Mayerhofer
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
David
D
Nahey
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Christopher
C
Stauthammer
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Maxie
M
Krüger
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Anthony
A
Tobias
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
M Gerard
MG
O'Sullivan
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Josh
J
Parker
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Jun
J
Tian
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Adam J
AJ
Case
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Matthew C
MC
Zimmerman
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011301:Preoptic Area / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D016277:Ventricular Function, Left / Q000502:physiology*
D013482:Superoxide Dismutase
heart failure; median preoptic nucleus; myocardial infarction; noradrenaline; superoxide dismutase