Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction
Background and aims: We aim to identify significant transcriptome alterations of vascular smooth muscle cells (VSMCs) in the aortic wall of myocardial infarction (MI) patients. Providing a robust transcriptomic signature, we aim to highlight the most likely aberrant pathway(s) in MI VSMCs. Methods a...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/104138 http://hdl.handle.net/10220/47805 |
| _version_ | 1811688086131703808 |
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| author | Wongsurawat, Thidathip Woo, Chin Cheng Giannakakis, Antonis Lin, Xiao Yun Cheow, Esther Sok Hwee Lee, Chuen Neng Richards, Mark Sze, Siu Kwan Nookaew, Intawat Kuznetsov, Vladimir Andreevich Sorokin, Vitaly |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Wongsurawat, Thidathip Woo, Chin Cheng Giannakakis, Antonis Lin, Xiao Yun Cheow, Esther Sok Hwee Lee, Chuen Neng Richards, Mark Sze, Siu Kwan Nookaew, Intawat Kuznetsov, Vladimir Andreevich Sorokin, Vitaly |
| author_sort | Wongsurawat, Thidathip |
| collection | NTU |
| description | Background and aims: We aim to identify significant transcriptome alterations of vascular smooth muscle cells (VSMCs) in the aortic wall of myocardial infarction (MI) patients. Providing a robust transcriptomic signature, we aim to highlight the most likely aberrant pathway(s) in MI VSMCs. Methods and results: Laser-captured microdissection (LCM) was used to obtain VSMCs from aortic wall tissues harvested during coronary artery bypass surgery. Microarray gene analysis was applied to analyse VSMCs from 17 MI and 19 non-MI patients. Prediction Analysis of Microarray (PAM) identified 370 genes that significantly discriminated MI and non-MI samples and were enriched in genes responsible for muscle development, differentiation and phenotype regulation. Incorporation of gene ontology (GO) led to the identification of a 21-gene VSMCs-associated classifier that discriminated between MI and non-MI patients with 92% accuracy. The mass spectrometry-based iTRAQ analysis of the MI and non-MI samples revealed 94 proteins significantly differentiating these tissues. Ingenuity Pathway Analysis (IPA) of 370 genes revealed top pathways associated with hypoxia signaling in the cardiovascular system. Enrichment analysis of these proteins suggested an activation of the superoxide radical degradation pathway. An integrated transcriptome-proteome pathway analysis revealed that superoxide radical degradation pathway remained the most implicated pathway. The intersection of the top candidate molecules from the transcriptome and proteome highlighted superoxide dismutase (SOD1) overexpression. Conclusions: We provided a novel 21-gene VSMCs-associated MI classifier in reference to significant VSMCs transcriptome alterations that, in combination with proteomics data, suggests the activation of superoxide radical degradation pathway in VSMCs of MI patients. |
| first_indexed | 2024-10-01T05:26:37Z |
| format | Journal Article |
| id | ntu-10356/104138 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:26:37Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1041382020-03-07T11:50:49Z Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction Wongsurawat, Thidathip Woo, Chin Cheng Giannakakis, Antonis Lin, Xiao Yun Cheow, Esther Sok Hwee Lee, Chuen Neng Richards, Mark Sze, Siu Kwan Nookaew, Intawat Kuznetsov, Vladimir Andreevich Sorokin, Vitaly School of Biological Sciences School of Computer Science and Engineering Myocardial Infarction DRNTU::Science::Biological sciences Vascular Smooth Muscle Cells Background and aims: We aim to identify significant transcriptome alterations of vascular smooth muscle cells (VSMCs) in the aortic wall of myocardial infarction (MI) patients. Providing a robust transcriptomic signature, we aim to highlight the most likely aberrant pathway(s) in MI VSMCs. Methods and results: Laser-captured microdissection (LCM) was used to obtain VSMCs from aortic wall tissues harvested during coronary artery bypass surgery. Microarray gene analysis was applied to analyse VSMCs from 17 MI and 19 non-MI patients. Prediction Analysis of Microarray (PAM) identified 370 genes that significantly discriminated MI and non-MI samples and were enriched in genes responsible for muscle development, differentiation and phenotype regulation. Incorporation of gene ontology (GO) led to the identification of a 21-gene VSMCs-associated classifier that discriminated between MI and non-MI patients with 92% accuracy. The mass spectrometry-based iTRAQ analysis of the MI and non-MI samples revealed 94 proteins significantly differentiating these tissues. Ingenuity Pathway Analysis (IPA) of 370 genes revealed top pathways associated with hypoxia signaling in the cardiovascular system. Enrichment analysis of these proteins suggested an activation of the superoxide radical degradation pathway. An integrated transcriptome-proteome pathway analysis revealed that superoxide radical degradation pathway remained the most implicated pathway. The intersection of the top candidate molecules from the transcriptome and proteome highlighted superoxide dismutase (SOD1) overexpression. Conclusions: We provided a novel 21-gene VSMCs-associated MI classifier in reference to significant VSMCs transcriptome alterations that, in combination with proteomics data, suggests the activation of superoxide radical degradation pathway in VSMCs of MI patients. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2019-03-13T07:33:53Z 2019-12-06T21:27:17Z 2019-03-13T07:33:53Z 2019-12-06T21:27:17Z 2018 Journal Article Wongsurawat, T., Woo, C. C., Giannakakis, A., Lin, X. Y., Cheow, E. S. H., Lee, C. N., . . . Sorokin, V. (2018). Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction. Atherosclerosis, 271, 237-244. doi:10.1016/j.atherosclerosis.2018.01.024 0021-9150 https://hdl.handle.net/10356/104138 http://hdl.handle.net/10220/47805 10.1016/j.atherosclerosis.2018.01.024 en Atherosclerosis © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 8 p. application/pdf |
| spellingShingle | Myocardial Infarction DRNTU::Science::Biological sciences Vascular Smooth Muscle Cells Wongsurawat, Thidathip Woo, Chin Cheng Giannakakis, Antonis Lin, Xiao Yun Cheow, Esther Sok Hwee Lee, Chuen Neng Richards, Mark Sze, Siu Kwan Nookaew, Intawat Kuznetsov, Vladimir Andreevich Sorokin, Vitaly Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title | Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title_full | Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title_fullStr | Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title_full_unstemmed | Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title_short | Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| title_sort | distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction |
| topic | Myocardial Infarction DRNTU::Science::Biological sciences Vascular Smooth Muscle Cells |
| url | https://hdl.handle.net/10356/104138 http://hdl.handle.net/10220/47805 |
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