The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage.
BACKGROUND: Emerging evidence showed the beneficial effect of acidic fibroblast growth factor (aFGF) on heart diseases. The present study investigated whether non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the underlying mechanisms, if any. METHODOLOGY/PRINCIPAL FINDINGS: Type...
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| Format: | Article |
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Public Library of Science (PLoS)
2013-01-01
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| Online Access: | http://europepmc.org/articles/PMC3857250?pdf=render |
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| author | Chi Zhang Linbo Zhang Shali Chen Biao Feng Xuemian Lu Yang Bai Guang Liang Yi Tan Minglong Shao Melissa Skibba Litai Jin Xiaokun Li Subrata Chakrabarti Lu Cai |
| author_facet | Chi Zhang Linbo Zhang Shali Chen Biao Feng Xuemian Lu Yang Bai Guang Liang Yi Tan Minglong Shao Melissa Skibba Litai Jin Xiaokun Li Subrata Chakrabarti Lu Cai |
| author_sort | Chi Zhang |
| collection | DOAJ |
| description | BACKGROUND: Emerging evidence showed the beneficial effect of acidic fibroblast growth factor (aFGF) on heart diseases. The present study investigated whether non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the underlying mechanisms, if any. METHODOLOGY/PRINCIPAL FINDINGS: Type 1 diabetes was induced in mice by multiple intraperitoneal injections of low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without nm-aFGF at 10 µg/kg daily for 1 and 6 months. Blood pressure and cardiac function were assessed. Cardiac H9c2 cell, human microvascular endothelial cells, and rat cardiomyocytes were exposed to high glucose (25 mM) for mimicking an in vitro diabetic condition for mechanistic studies. Oxidative stress, DNA damage, cardiac hypertrophy and fibrosis were assessed by real-time qPCR, immunofluorescent staining, Western blotting, and pathological examination. Nm-aFGF significantly prevented diabetes-induced hypertension and cardiac dysfunction at 6 months. Mechanistic studies demonstrated that nm-aFGF showed the similar preventive effect as the native aFGF on high glucose-induced oxidative stress (increase generation of reactive oxygen species) and damage (cellular DNA oxidation), cell hypertrophy, and fibrotic response (increased mRNA expression of fibronectin) in three kinds of cells. These in vitro findings were recaptured by examining the heart of the diabetic mice with and without nm-aFGF. CONCLUSIONS: These results suggest that nm-aFGF can prevent diabetic cardiomyopathy, probably through attenuation of cardiac oxidative stress, hypertrophy, and fibrosis. |
| first_indexed | 2024-12-11T22:03:16Z |
| format | Article |
| id | doaj.art-50230d34132f4e99905d3c874a390939 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:03:16Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-50230d34132f4e99905d3c874a3909392022-12-22T00:49:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8228710.1371/journal.pone.0082287The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage.Chi ZhangLinbo ZhangShali ChenBiao FengXuemian LuYang BaiGuang LiangYi TanMinglong ShaoMelissa SkibbaLitai JinXiaokun LiSubrata ChakrabartiLu CaiBACKGROUND: Emerging evidence showed the beneficial effect of acidic fibroblast growth factor (aFGF) on heart diseases. The present study investigated whether non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the underlying mechanisms, if any. METHODOLOGY/PRINCIPAL FINDINGS: Type 1 diabetes was induced in mice by multiple intraperitoneal injections of low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without nm-aFGF at 10 µg/kg daily for 1 and 6 months. Blood pressure and cardiac function were assessed. Cardiac H9c2 cell, human microvascular endothelial cells, and rat cardiomyocytes were exposed to high glucose (25 mM) for mimicking an in vitro diabetic condition for mechanistic studies. Oxidative stress, DNA damage, cardiac hypertrophy and fibrosis were assessed by real-time qPCR, immunofluorescent staining, Western blotting, and pathological examination. Nm-aFGF significantly prevented diabetes-induced hypertension and cardiac dysfunction at 6 months. Mechanistic studies demonstrated that nm-aFGF showed the similar preventive effect as the native aFGF on high glucose-induced oxidative stress (increase generation of reactive oxygen species) and damage (cellular DNA oxidation), cell hypertrophy, and fibrotic response (increased mRNA expression of fibronectin) in three kinds of cells. These in vitro findings were recaptured by examining the heart of the diabetic mice with and without nm-aFGF. CONCLUSIONS: These results suggest that nm-aFGF can prevent diabetic cardiomyopathy, probably through attenuation of cardiac oxidative stress, hypertrophy, and fibrosis.http://europepmc.org/articles/PMC3857250?pdf=render |
| spellingShingle | Chi Zhang Linbo Zhang Shali Chen Biao Feng Xuemian Lu Yang Bai Guang Liang Yi Tan Minglong Shao Melissa Skibba Litai Jin Xiaokun Li Subrata Chakrabarti Lu Cai The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. PLoS ONE |
| title | The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. |
| title_full | The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. |
| title_fullStr | The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. |
| title_full_unstemmed | The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. |
| title_short | The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. |
| title_sort | prevention of diabetic cardiomyopathy by non mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage |
| url | http://europepmc.org/articles/PMC3857250?pdf=render |
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