LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes
Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-in...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.747802/full |
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| author | Cuizhi Li Huafeng Song Chunlin Chen Shaoxian Chen Qiyu Zhang Dehui Liu Jinglong Li Haojian Dong Yueheng Wu Youbin Liu |
| author_facet | Cuizhi Li Huafeng Song Chunlin Chen Shaoxian Chen Qiyu Zhang Dehui Liu Jinglong Li Haojian Dong Yueheng Wu Youbin Liu |
| author_sort | Cuizhi Li |
| collection | DOAJ |
| description | Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage. |
| first_indexed | 2024-12-19T20:47:44Z |
| format | Article |
| id | doaj.art-30ce53f292994b00b474b07dfd17ebc0 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-19T20:47:44Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-30ce53f292994b00b474b07dfd17ebc02022-12-21T20:06:10ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-09-01810.3389/fcvm.2021.747802747802LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in CardiomyocytesCuizhi Li0Huafeng Song1Chunlin Chen2Shaoxian Chen3Qiyu Zhang4Dehui Liu5Jinglong Li6Haojian Dong7Yueheng Wu8Youbin Liu9Department of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangdong Provincial People's Hospital, Guangzhou, ChinaGuangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, ChinaObjective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.https://www.frontiersin.org/articles/10.3389/fcvm.2021.747802/fulllncRNAPVT1myocardial ischemia reperfusionpyroptosisgasdermin D |
| spellingShingle | Cuizhi Li Huafeng Song Chunlin Chen Shaoxian Chen Qiyu Zhang Dehui Liu Jinglong Li Haojian Dong Yueheng Wu Youbin Liu LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes Frontiers in Cardiovascular Medicine lncRNA PVT1 myocardial ischemia reperfusion pyroptosis gasdermin D |
| title | LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes |
| title_full | LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes |
| title_fullStr | LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes |
| title_full_unstemmed | LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes |
| title_short | LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes |
| title_sort | lncrna pvt1 knockdown ameliorates myocardial ischemia reperfusion damage via suppressing gasdermin d mediated pyroptosis in cardiomyocytes |
| topic | lncRNA PVT1 myocardial ischemia reperfusion pyroptosis gasdermin D |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.747802/full |
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