Extracellular superoxide dismutase protects the heart against oxidative stress and hypertrophy after myocardial infarction

Elza D. van Deel; Zhongbing Lu; Xin Xu; Guangshuo Zhu; Xinli Hu; Tim D. Oury; Robert J. Bache; Dirk J. Duncker; Yingjie Chen

doi:10.1016/j.freeradbiomed.2007.12.007

Extracellular superoxide dismutase protects the heart against oxidative stress and hypertrophy after myocardial infarction

Elza D. van Deel, Zhongbing Lu, Xin Xu, Guangshuo Zhu, Xinli Hu, Tim D. Oury, Robert J. Bache, Dirk J. Duncker, Yingjie Chen

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

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Abstract

Extracellular superoxide dismutase (EC-SOD) contributes only a small fraction to total SOD activity in the heart but is strategically located to scavenge free radicals in the extracellular compartment. EC-SOD expression is decreased in myocardial-infarction (MI)-induced heart failure, but whether EC-SOD can abrogate oxidative stress or modify MI-induced ventricular remodeling has not been previously studied. Consequently, the effects of EC-SOD gene deficiency (EC-SOD KO) on left ventricular (LV) oxidative stress, hypertrophy, and fibrosis were studied in EC-SOD KO and wild-type mice under control conditions, and at 4 and 8 weeks after permanent coronary artery ligation. EC-SOD KO had no detectable effect on LV function in normal hearts but caused small but significant increases of LV fibrosis. At 8 weeks after MI, EC-SOD KO mice developed significantly more LV hypertrophy (LV mass increased 1.64-fold in KO mice compared to 1.35-fold in wild-type mice; p < 0.01) and more fibrosis and myocyte hypertrophy which was more prominent in the peri-infarct region than in the remote myocardium. EC-SOD KO mice had greater increases of nitrotyrosine in the peri-infarct myocardium, and this was associated with a greater reduction of LV ejection fraction, a greater decrease of sarcoplasmic or endoplasmic reticulum calcium²⁺ ATPase, and a greater increase of atrial natriuretic peptide in the peri-infarct zone compared to wild-type mice. EC-SOD KO was associated with more increases of phosphorylated p38 (p-p38^{Thr180/Tyr182}), p42/44 extracellular signal-regulated kinase (p-Erk^{Thr202/Tyr204}), and c-Jun N-terminal kinase (p-JNK^{Thr183/Tyr185}) both under control conditions and after MI, indicating that EC-SOD KO increases activation of mitogen-activated protein kinase signaling pathways. These findings demonstrate that EC-SOD plays an important role in protecting the heart against oxidative stress and infarction-induced ventricular hypertrophy.

Original language	English (US)
Pages (from-to)	1305-1313
Number of pages	9
Journal	Free Radical Biology and Medicine
Volume	44
Issue number	7
DOIs	https://doi.org/10.1016/j.freeradbiomed.2007.12.007
State	Published - Apr 1 2008

Bibliographical note

Funding Information:
We are grateful to Dr. Stefan Marklund of Umea University, Umea, Sweden for supply of breeding pairs of EC-SOD −/− mice. This study was supported by NHLBI Grants HL71790 (Y.C.), HL21872 (R.J.B.), and HL63700 (T.D.O.) from the National Institutes of Health.

Keywords

Extracellular matrix
Hypertrophy
Infarction
Oxygen radicals
Remodeling

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Extracellular superoxide dismutase protects the heart against oxidative stress and hypertrophy after myocardial infarction",

abstract = "Extracellular superoxide dismutase (EC-SOD) contributes only a small fraction to total SOD activity in the heart but is strategically located to scavenge free radicals in the extracellular compartment. EC-SOD expression is decreased in myocardial-infarction (MI)-induced heart failure, but whether EC-SOD can abrogate oxidative stress or modify MI-induced ventricular remodeling has not been previously studied. Consequently, the effects of EC-SOD gene deficiency (EC-SOD KO) on left ventricular (LV) oxidative stress, hypertrophy, and fibrosis were studied in EC-SOD KO and wild-type mice under control conditions, and at 4 and 8 weeks after permanent coronary artery ligation. EC-SOD KO had no detectable effect on LV function in normal hearts but caused small but significant increases of LV fibrosis. At 8 weeks after MI, EC-SOD KO mice developed significantly more LV hypertrophy (LV mass increased 1.64-fold in KO mice compared to 1.35-fold in wild-type mice; p < 0.01) and more fibrosis and myocyte hypertrophy which was more prominent in the peri-infarct region than in the remote myocardium. EC-SOD KO mice had greater increases of nitrotyrosine in the peri-infarct myocardium, and this was associated with a greater reduction of LV ejection fraction, a greater decrease of sarcoplasmic or endoplasmic reticulum calcium2+ ATPase, and a greater increase of atrial natriuretic peptide in the peri-infarct zone compared to wild-type mice. EC-SOD KO was associated with more increases of phosphorylated p38 (p-p38Thr180/Tyr182), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204), and c-Jun N-terminal kinase (p-JNKThr183/Tyr185) both under control conditions and after MI, indicating that EC-SOD KO increases activation of mitogen-activated protein kinase signaling pathways. These findings demonstrate that EC-SOD plays an important role in protecting the heart against oxidative stress and infarction-induced ventricular hypertrophy.",

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AU - Oury, Tim D.

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AU - Duncker, Dirk J.

AU - Chen, Yingjie

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N2 - Extracellular superoxide dismutase (EC-SOD) contributes only a small fraction to total SOD activity in the heart but is strategically located to scavenge free radicals in the extracellular compartment. EC-SOD expression is decreased in myocardial-infarction (MI)-induced heart failure, but whether EC-SOD can abrogate oxidative stress or modify MI-induced ventricular remodeling has not been previously studied. Consequently, the effects of EC-SOD gene deficiency (EC-SOD KO) on left ventricular (LV) oxidative stress, hypertrophy, and fibrosis were studied in EC-SOD KO and wild-type mice under control conditions, and at 4 and 8 weeks after permanent coronary artery ligation. EC-SOD KO had no detectable effect on LV function in normal hearts but caused small but significant increases of LV fibrosis. At 8 weeks after MI, EC-SOD KO mice developed significantly more LV hypertrophy (LV mass increased 1.64-fold in KO mice compared to 1.35-fold in wild-type mice; p < 0.01) and more fibrosis and myocyte hypertrophy which was more prominent in the peri-infarct region than in the remote myocardium. EC-SOD KO mice had greater increases of nitrotyrosine in the peri-infarct myocardium, and this was associated with a greater reduction of LV ejection fraction, a greater decrease of sarcoplasmic or endoplasmic reticulum calcium2+ ATPase, and a greater increase of atrial natriuretic peptide in the peri-infarct zone compared to wild-type mice. EC-SOD KO was associated with more increases of phosphorylated p38 (p-p38Thr180/Tyr182), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204), and c-Jun N-terminal kinase (p-JNKThr183/Tyr185) both under control conditions and after MI, indicating that EC-SOD KO increases activation of mitogen-activated protein kinase signaling pathways. These findings demonstrate that EC-SOD plays an important role in protecting the heart against oxidative stress and infarction-induced ventricular hypertrophy.

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Extracellular superoxide dismutase protects the heart against oxidative stress and hypertrophy after myocardial infarction

Abstract

Bibliographical note

Keywords

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