Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients
The obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for the etiopathology of AMI have not been...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1293393/full |
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| author | Yuning Tang Yuning Tang Yuning Tang Yuning Tang Yongxiang Wang Yongxiang Wang Yongxiang Wang Shengxiang Wang Runqing Wang Runqing Wang Runqing Wang Jin Xu Jin Xu Jin Xu Yu Peng Yu Peng Yu Peng Liqiong Ding Liqiong Ding Liqiong Ding Jing Zhao Jing Zhao Jing Zhao Jing Zhao Gang Zhou Shougang Sun Zheng Zhang Zheng Zhang Zheng Zhang Zheng Zhang |
| author_facet | Yuning Tang Yuning Tang Yuning Tang Yuning Tang Yongxiang Wang Yongxiang Wang Yongxiang Wang Shengxiang Wang Runqing Wang Runqing Wang Runqing Wang Jin Xu Jin Xu Jin Xu Yu Peng Yu Peng Yu Peng Liqiong Ding Liqiong Ding Liqiong Ding Jing Zhao Jing Zhao Jing Zhao Jing Zhao Gang Zhou Shougang Sun Zheng Zhang Zheng Zhang Zheng Zhang Zheng Zhang |
| author_sort | Yuning Tang |
| collection | DOAJ |
| description | The obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for the etiopathology of AMI have not been investigated in detail. This study aimed to explore the relationship between DNA methylation and pathologically altered gene expression profile in human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation (OGD), and its clinical implications in AMI patients. The Illumina Infinium MethylationEPIC BeadChip assay was used to explore the genome-wide DNA methylation profile using the Novaseq6000 platform for mRNA sequencing in 3 pairs of HUVEC-OGD and control samples. GO and KEGG pathway enrichment analyses, as well as correlation, causal inference test (CIT), and protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget sequencing as well as qRT-PCR. ELISA was used to detect four target molecules associated with the progression of AMI. A total of 2,524 differentially expressed genes (DEGs) and 22,148 differentially methylated positions (DMPs) corresponding to 6,642 differentially methylated genes (DMGs) were screened (|Δβ|>0.1 and detection p < 0.05). After GO, KEGG, correlation, CIT, and PPI analyses, 441 genes were filtered. qRT-PCR confirmed the overexpression of VEGFA, CCL2, TSP-1, SQSTM1, BCL2L11, and TIMP3 genes, and downregulation of MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, and MEIS1. DNA fragments BDNF_1_ (r = 0.931, p < 0.0001) and SQSTM1_2_NEW (r = 0.758, p = 0.0043) were positively correlated with the expressions of corresponding genes, and MYC_1_ (r = −0.8245, p = 0.001) was negatively correlated. Furthermore, ELISA confirmed TNFSF10 and BDNF were elevated in the peripheral blood of AMI patients (p = 0.0284 and p = 0.0142, respectively). Combined sequencing from in vitro cellular assays with clinical samples, aiming to establish the potential causal chain of the causal factor (DNA methylation) - mediator (mRNA)—cell outcome (endothelial cell ischemic-hypoxic injury)-clinical outcome (AMI), our study identified promising OGD-specific genes, which provided a solid basis for screening fundamental diagnostic and prognostic biomarkers of coronary endothelial cell injury of AMI. Moreover, it furnished the first evidence that during ischemia and hypoxia, the expression of BNDF was regulated by DNA methylation in endothelial cells and elevated in peripheral blood. |
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| language | English |
| last_indexed | 2024-03-09T02:12:16Z |
| publishDate | 2023-12-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-f5cdce657f454e11bb5a71f3e8b9124d2023-12-07T08:55:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-12-011410.3389/fgene.2023.12933931293393Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patientsYuning Tang0Yuning Tang1Yuning Tang2Yuning Tang3Yongxiang Wang4Yongxiang Wang5Yongxiang Wang6Shengxiang Wang7Runqing Wang8Runqing Wang9Runqing Wang10Jin Xu11Jin Xu12Jin Xu13Yu Peng14Yu Peng15Yu Peng16Liqiong Ding17Liqiong Ding18Liqiong Ding19Jing Zhao20Jing Zhao21Jing Zhao22Jing Zhao23Gang Zhou24Shougang Sun25Zheng Zhang26Zheng Zhang27Zheng Zhang28Zheng Zhang29The First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaDepartment of Cardiology, Lanzhou University Second Hospital, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaHeart Center, The First Hospital of Lanzhou University, Lanzhou, ChinaSchool of Life and Environmental Sciences, Minzu University of China, Beijing, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaHeart Center, The First Hospital of Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaHeart Center, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaHeart Center, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Cardiology, Lanzhou University Second Hospital, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaGansu Key Laboratory of Cardiovascular Diseases, The First Hospital of Lanzhou University, Lanzhou, ChinaCardiovascular Clinical Research Center of Gansu Province, Lanzhou, ChinaHeart Center, The First Hospital of Lanzhou University, Lanzhou, ChinaThe obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for the etiopathology of AMI have not been investigated in detail. This study aimed to explore the relationship between DNA methylation and pathologically altered gene expression profile in human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation (OGD), and its clinical implications in AMI patients. The Illumina Infinium MethylationEPIC BeadChip assay was used to explore the genome-wide DNA methylation profile using the Novaseq6000 platform for mRNA sequencing in 3 pairs of HUVEC-OGD and control samples. GO and KEGG pathway enrichment analyses, as well as correlation, causal inference test (CIT), and protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget sequencing as well as qRT-PCR. ELISA was used to detect four target molecules associated with the progression of AMI. A total of 2,524 differentially expressed genes (DEGs) and 22,148 differentially methylated positions (DMPs) corresponding to 6,642 differentially methylated genes (DMGs) were screened (|Δβ|>0.1 and detection p < 0.05). After GO, KEGG, correlation, CIT, and PPI analyses, 441 genes were filtered. qRT-PCR confirmed the overexpression of VEGFA, CCL2, TSP-1, SQSTM1, BCL2L11, and TIMP3 genes, and downregulation of MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, and MEIS1. DNA fragments BDNF_1_ (r = 0.931, p < 0.0001) and SQSTM1_2_NEW (r = 0.758, p = 0.0043) were positively correlated with the expressions of corresponding genes, and MYC_1_ (r = −0.8245, p = 0.001) was negatively correlated. Furthermore, ELISA confirmed TNFSF10 and BDNF were elevated in the peripheral blood of AMI patients (p = 0.0284 and p = 0.0142, respectively). Combined sequencing from in vitro cellular assays with clinical samples, aiming to establish the potential causal chain of the causal factor (DNA methylation) - mediator (mRNA)—cell outcome (endothelial cell ischemic-hypoxic injury)-clinical outcome (AMI), our study identified promising OGD-specific genes, which provided a solid basis for screening fundamental diagnostic and prognostic biomarkers of coronary endothelial cell injury of AMI. Moreover, it furnished the first evidence that during ischemia and hypoxia, the expression of BNDF was regulated by DNA methylation in endothelial cells and elevated in peripheral blood.https://www.frontiersin.org/articles/10.3389/fgene.2023.1293393/fullDNA methylationoxygen-glucose deprivationacute myocardial infarctionmRNA sequencebrain-derived neurotrophic factortumor necrosis factor superfamily member 10 |
| spellingShingle | Yuning Tang Yuning Tang Yuning Tang Yuning Tang Yongxiang Wang Yongxiang Wang Yongxiang Wang Shengxiang Wang Runqing Wang Runqing Wang Runqing Wang Jin Xu Jin Xu Jin Xu Yu Peng Yu Peng Yu Peng Liqiong Ding Liqiong Ding Liqiong Ding Jing Zhao Jing Zhao Jing Zhao Jing Zhao Gang Zhou Shougang Sun Zheng Zhang Zheng Zhang Zheng Zhang Zheng Zhang Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients Frontiers in Genetics DNA methylation oxygen-glucose deprivation acute myocardial infarction mRNA sequence brain-derived neurotrophic factor tumor necrosis factor superfamily member 10 |
| title | Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients |
| title_full | Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients |
| title_fullStr | Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients |
| title_full_unstemmed | Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients |
| title_short | Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients |
| title_sort | methylation and transcriptomic expression profiles of huvec in the oxygen and glucose deprivation model and its clinical implications in ami patients |
| topic | DNA methylation oxygen-glucose deprivation acute myocardial infarction mRNA sequence brain-derived neurotrophic factor tumor necrosis factor superfamily member 10 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1293393/full |
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