Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress
Hypoglycemic agents have been shown to reduce the incidence of atrial fibrillation (AF) in patients with diabetes mellitus. Azoramide is a novel anti-diabetic agent which protects cells against endoplasmic reticulum (ER) stress; however, the cardioprotective effect of azoramide against AF is not cle...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Stem Cell Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506122000356 |
| _version_ | 1818338535547076608 |
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| author | Weilun Miao Jiaojiao Shi Jiayi Huang Yongpin Lin Chang Cui Yue Zhu Bingyu Zheng Mingfang Li Qi Jiang Minglong Chen |
| author_facet | Weilun Miao Jiaojiao Shi Jiayi Huang Yongpin Lin Chang Cui Yue Zhu Bingyu Zheng Mingfang Li Qi Jiang Minglong Chen |
| author_sort | Weilun Miao |
| collection | DOAJ |
| description | Hypoglycemic agents have been shown to reduce the incidence of atrial fibrillation (AF) in patients with diabetes mellitus. Azoramide is a novel anti-diabetic agent which protects cells against endoplasmic reticulum (ER) stress; however, the cardioprotective effect of azoramide against AF is not clear. In this study, we aimed to investigate the protective effect of azoramide in human iPS-derived atrial myocytes (a-iCMs) against injury induced by high-frequency electrical stimulation. Human-induced pluripotent stem cells were differentiated into a-iCMs by treatment of retinoic acid. The tachypacing group was subjected to 7 Hz tachypacing for 48 h. Azoramide was preconditioned 2-hours before tachypacing. a-iCMs expressed atria-specific genes and the characteristics of the action potential were analogous to those of human atrial myocytes. Tachypacing induced disorder of intracellular calcium homeostasis, apoptosis, depressed ATP level, and severer myofilament dissolution. MetaboAnalysis revealed that tachypacing induced remarkable changes in metabolites involved in energy, amino acid, and glucose metabolism, whereas there was no significant effect on lipid metabolism. Azoramide pretreatment partly alleviated tachypacing-induced calcium dyshomeostasis, ATP consumption, and accelerated apoptosis, which was likely achieved by regulating the PERK/CHOP/CaMKII pathway. Azoramide protected atrial myocytes against injury induced by high-frequency electrical stimulation by regulating ER stress, which may inhibit cell apoptosis and calcium dyshomeostasis via the PERK/CHOP/CaMKII pathway. |
| first_indexed | 2024-12-13T15:12:39Z |
| format | Article |
| id | doaj.art-538390ae331e4169b0e047e3eb7916df |
| institution | Directory Open Access Journal |
| issn | 1873-5061 |
| language | English |
| last_indexed | 2024-12-13T15:12:39Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-538390ae331e4169b0e047e3eb7916df2022-12-21T23:40:50ZengElsevierStem Cell Research1873-50612022-04-0160102686Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stressWeilun Miao0Jiaojiao Shi1Jiayi Huang2Yongpin Lin3Chang Cui4Yue Zhu5Bingyu Zheng6Mingfang Li7Qi Jiang8Minglong Chen9Department of Cardiology, Huashan Hospital Affiliated to Fudan University, Shanghai 200000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, NanJing Pukou Central Hospital, Nanjing 210000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, ChinaDepartment of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou 213000, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China; Correspondence to: Minglong Chen M.D. & Ph.D. & FHRS Professor of Medicine, Department of Cardiology, Jiangsu Province Hospital, Nanjing Medical University, Nanjing 210000, China.Hypoglycemic agents have been shown to reduce the incidence of atrial fibrillation (AF) in patients with diabetes mellitus. Azoramide is a novel anti-diabetic agent which protects cells against endoplasmic reticulum (ER) stress; however, the cardioprotective effect of azoramide against AF is not clear. In this study, we aimed to investigate the protective effect of azoramide in human iPS-derived atrial myocytes (a-iCMs) against injury induced by high-frequency electrical stimulation. Human-induced pluripotent stem cells were differentiated into a-iCMs by treatment of retinoic acid. The tachypacing group was subjected to 7 Hz tachypacing for 48 h. Azoramide was preconditioned 2-hours before tachypacing. a-iCMs expressed atria-specific genes and the characteristics of the action potential were analogous to those of human atrial myocytes. Tachypacing induced disorder of intracellular calcium homeostasis, apoptosis, depressed ATP level, and severer myofilament dissolution. MetaboAnalysis revealed that tachypacing induced remarkable changes in metabolites involved in energy, amino acid, and glucose metabolism, whereas there was no significant effect on lipid metabolism. Azoramide pretreatment partly alleviated tachypacing-induced calcium dyshomeostasis, ATP consumption, and accelerated apoptosis, which was likely achieved by regulating the PERK/CHOP/CaMKII pathway. Azoramide protected atrial myocytes against injury induced by high-frequency electrical stimulation by regulating ER stress, which may inhibit cell apoptosis and calcium dyshomeostasis via the PERK/CHOP/CaMKII pathway.http://www.sciencedirect.com/science/article/pii/S1873506122000356Atrial fibrillation1Human induced pluripotent stem cell2Electrical tachypacing3Azoramide5ER stress |
| spellingShingle | Weilun Miao Jiaojiao Shi Jiayi Huang Yongpin Lin Chang Cui Yue Zhu Bingyu Zheng Mingfang Li Qi Jiang Minglong Chen Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress Stem Cell Research Atrial fibrillation1 Human induced pluripotent stem cell2 Electrical tachypacing3 Azoramide5 ER stress |
| title | Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| title_full | Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| title_fullStr | Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| title_full_unstemmed | Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| title_short | Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| title_sort | azoramide ameliorated tachypacing induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress |
| topic | Atrial fibrillation1 Human induced pluripotent stem cell2 Electrical tachypacing3 Azoramide5 ER stress |
| url | http://www.sciencedirect.com/science/article/pii/S1873506122000356 |
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