Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes
Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms.Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00855/full |
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doaj-39363a2a05ac44b790d3a95f50b4b2ca |
|---|---|
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Meng Wu Meng Wu Yeping Yang Meng Wang Fangfang Zeng Qin Li Wenjuan Liu Shizhe Guo Min He Min He Yi Wang Jie Huang Linuo Zhou Yiming Li Yiming Li Ji Hu Wei Gong Zhaoyun Zhang Zhaoyun Zhang |
| spellingShingle |
Meng Wu Meng Wu Yeping Yang Meng Wang Fangfang Zeng Qin Li Wenjuan Liu Shizhe Guo Min He Min He Yi Wang Jie Huang Linuo Zhou Yiming Li Yiming Li Ji Hu Wei Gong Zhaoyun Zhang Zhaoyun Zhang Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes Frontiers in Pharmacology pancreatic kallikrein diabetic cardiomyopathy kallikrein-kinin system fibrosis inflammation oxidative stress |
| author_facet |
Meng Wu Meng Wu Yeping Yang Meng Wang Fangfang Zeng Qin Li Wenjuan Liu Shizhe Guo Min He Min He Yi Wang Jie Huang Linuo Zhou Yiming Li Yiming Li Ji Hu Wei Gong Zhaoyun Zhang Zhaoyun Zhang |
| author_sort |
Meng Wu |
| title |
Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes |
| title_short |
Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes |
| title_full |
Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes |
| title_fullStr |
Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes |
| title_full_unstemmed |
Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes |
| title_sort |
exogenous pancreatic kallikrein improves diabetic cardiomyopathy in streptozotocin-induced diabetes |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Pharmacology |
| issn |
1663-9812 |
| publishDate |
2018-08-01 |
| description |
Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms.Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-β1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of IκB-α, an inhibitive element of heterotrimer nuclear factor kappa B (NF-κB). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment.Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel. |
| topic |
pancreatic kallikrein diabetic cardiomyopathy kallikrein-kinin system fibrosis inflammation oxidative stress |
| url |
https://www.frontiersin.org/article/10.3389/fphar.2018.00855/full |
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doaj-39363a2a05ac44b790d3a95f50b4b2ca2020-11-24T22:08:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-08-01910.3389/fphar.2018.00855382387Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced DiabetesMeng Wu0Meng Wu1Yeping Yang2Meng Wang3Fangfang Zeng4Qin Li5Wenjuan Liu6Shizhe Guo7Min He8Min He9Yi Wang10Jie Huang11Linuo Zhou12Yiming Li13Yiming Li14Ji Hu15Wei Gong16Zhaoyun Zhang17Zhaoyun Zhang18Division of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaInstitute of Endocrinology and Diabetology, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaChangzhou Qianhong Biopharma Co., Ltd., Changzhou, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaInstitute of Endocrinology and Diabetology, Fudan University, Shanghai, ChinaDepartment of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaDivision of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, ChinaInstitute of Endocrinology and Diabetology, Fudan University, Shanghai, ChinaAims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms.Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-β1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of IκB-α, an inhibitive element of heterotrimer nuclear factor kappa B (NF-κB). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment.Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel.https://www.frontiersin.org/article/10.3389/fphar.2018.00855/fullpancreatic kallikreindiabetic cardiomyopathykallikrein-kinin systemfibrosisinflammationoxidative stress |