PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway
Background: Phosphodiesterase-5 (PDE-5) inhibitors have been found to play an important cardio-protective role. This study aimed to clarify the inhibitory effects of PDE-5-silenced bone marrow mesenchymal stem cells (BMSCs) on high glucose-induced myocardial fibrosis and cardiomyocyte apoptosis. Met...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-07-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/7/10.31083/j.fbl2807155 |
| _version_ | 1797767964883156992 |
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| author | Qinghua Huang Jiangbo Ma Hui Wu Jieru Zhou Lei Jiang Xianming Fei |
| author_facet | Qinghua Huang Jiangbo Ma Hui Wu Jieru Zhou Lei Jiang Xianming Fei |
| author_sort | Qinghua Huang |
| collection | DOAJ |
| description | Background: Phosphodiesterase-5 (PDE-5) inhibitors have been found to play an important cardio-protective role. This study aimed to clarify the inhibitory effects of PDE-5-silenced bone marrow mesenchymal stem cells (BMSCs) on high glucose-induced myocardial fibrosis and cardiomyocyte apoptosis. Methods: Cardiomyocytes and fibroblasts of neonatal rats were treated with high glucose (HG), and co-cultured with PDE-5-overexpressed or -knocked down BMSCs. The viability and apoptosis as well as the levels of cytokines, Cardiac troponin I and Vimentin of cardiomyocytes and fibroblasts were studied. The expressions of PDE-5, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG), in both cells were evaluated. Results: BMSCs that silenced PDE-5 facilitated the viability of cardiomyocytes, decreased the viability of fibroblasts, and inhibited the apoptosis of cardiomyocytes and fibroblasts. The contents of collagen-I, collagen-III, tissue inhibitor of metalloproteinase (TIMP)-1 and Dermin in fibroblasts were decreased by the PDE-5 inhibitor, but the levels of matrix metalloproteinase (MMP)-1 in fibroblasts and troponin-I in cardiomyocytes were increased by the PDE-5 inhibitor. PDE-5 inhibitor also suppressed the expression of PDE-5 but up-regulated cGMP and PKG expression in cardiomyocytes and fibroblasts. Conclusions: PDE-5-inhibited BMSCs can decrease HG-induced myocardial fibrosis and cardiomyocyte apoptosis by activating the cGMP/PKG pathway, and may play a role in the prevention and treatment of diabetic cardiomyopathy. |
| first_indexed | 2024-03-12T20:47:38Z |
| format | Article |
| id | doaj.art-f133fe3b4da846da9fad00314196464f |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-12T20:47:38Z |
| publishDate | 2023-07-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-f133fe3b4da846da9fad00314196464f2023-08-01T07:41:59ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-07-0128715510.31083/j.fbl2807155S2768-6701(23)00766-9PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG PathwayQinghua Huang0Jiangbo Ma1Hui Wu2Jieru Zhou3Lei Jiang4Xianming Fei5Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, ChinaGeriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, ChinaGeriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, ChinaJinzhou Medical University, 121001 Jinzhou, Liaoning, ChinaLaboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, ChinaLaboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 310014 Hangzhou, Zhejiang, ChinaBackground: Phosphodiesterase-5 (PDE-5) inhibitors have been found to play an important cardio-protective role. This study aimed to clarify the inhibitory effects of PDE-5-silenced bone marrow mesenchymal stem cells (BMSCs) on high glucose-induced myocardial fibrosis and cardiomyocyte apoptosis. Methods: Cardiomyocytes and fibroblasts of neonatal rats were treated with high glucose (HG), and co-cultured with PDE-5-overexpressed or -knocked down BMSCs. The viability and apoptosis as well as the levels of cytokines, Cardiac troponin I and Vimentin of cardiomyocytes and fibroblasts were studied. The expressions of PDE-5, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG), in both cells were evaluated. Results: BMSCs that silenced PDE-5 facilitated the viability of cardiomyocytes, decreased the viability of fibroblasts, and inhibited the apoptosis of cardiomyocytes and fibroblasts. The contents of collagen-I, collagen-III, tissue inhibitor of metalloproteinase (TIMP)-1 and Dermin in fibroblasts were decreased by the PDE-5 inhibitor, but the levels of matrix metalloproteinase (MMP)-1 in fibroblasts and troponin-I in cardiomyocytes were increased by the PDE-5 inhibitor. PDE-5 inhibitor also suppressed the expression of PDE-5 but up-regulated cGMP and PKG expression in cardiomyocytes and fibroblasts. Conclusions: PDE-5-inhibited BMSCs can decrease HG-induced myocardial fibrosis and cardiomyocyte apoptosis by activating the cGMP/PKG pathway, and may play a role in the prevention and treatment of diabetic cardiomyopathy.https://www.imrpress.com/journal/FBL/28/7/10.31083/j.fbl2807155phosphodiesterase-5bmscsdiabetic cardiomyopathycgmp/pkg pathwaymyocardial fibrosiscardiomyocytes apoptosis |
| spellingShingle | Qinghua Huang Jiangbo Ma Hui Wu Jieru Zhou Lei Jiang Xianming Fei PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway Frontiers in Bioscience-Landmark phosphodiesterase-5 bmscs diabetic cardiomyopathy cgmp/pkg pathway myocardial fibrosis cardiomyocytes apoptosis |
| title | PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway |
| title_full | PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway |
| title_fullStr | PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway |
| title_full_unstemmed | PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway |
| title_short | PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway |
| title_sort | pde 5 inhibited bmscs alleviate high glucose induced myocardial fibrosis and cardiomyocyte apoptosis by activating the cgmp pkg pathway |
| topic | phosphodiesterase-5 bmscs diabetic cardiomyopathy cgmp/pkg pathway myocardial fibrosis cardiomyocytes apoptosis |
| url | https://www.imrpress.com/journal/FBL/28/7/10.31083/j.fbl2807155 |
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