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Overexpression of CuZnSOD in median preoptic nucleus improves cardiac function after myocardial infarction in the rat
Author(s) -
Collister John,
Hartnett Cristina,
Nahey David,
Stauthammer Christopher,
Kruger Maxie,
OSullivan Gerry,
Parker Josh,
Tian Jun,
Zimmerman Matthew
Publication year - 2013
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.27.1_supplement.919.6
Subject(s) - medicine , cardiac function curve , superoxide dismutase , ventricle , heart failure , myocardial infarction , cardiology , ejection fraction , reactive oxygen species , endocrinology , subfornical organ , pathophysiology , chemistry , angiotensin ii , oxidative stress , blood pressure , biochemistry
It has been shown that central overexpression of the superoxide scavenging enzyme, Cu/Zn superoxide dismutase (SOD), in the subfornical organ improves cardiac function in a mouse model of heart failure (HF). A downstream hypothalamic site, the median preoptic nucleus (MnPO), may act as a relay center for reactive oxygen species to act as mediators in the pathophysiology of HF. To test the hypothesis that elevated superoxide in the MnPO is related to the pathophysiology of HF and decreased cardiac function, we injected adenovirus encoding CuZnSOD (AdSOD, n=2) or control empty vector (AdE, n=3) 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 at 2 week intervals via echocardiography. Upon completion, rat brains were examined for SOD expression in MnPO via immunofluorescence and histopathological analyses of cardiac infarct size were conducted. Baseline (EF) ejection fractions (%) of AdSOD and AdE rats were 62±4 and 67±2, respectively. Two weeks after MI, EF was significantly decreased in both groups of rats (AdSOD: 38±3, AdE: 48±4). In contrast by 6 weeks post MI, EF had improved to 52±1 in AdSOD rats yet was only 41±6 in AdE rats. In conclusion, despite decreases in EF early after MI, overexpression of SOD in the MnPO was related to an improvement in left ventricular function 6 weeks post MI.