Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/104138
Title: Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction
Authors: 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
Keywords: Myocardial Infarction
DRNTU::Science::Biological sciences
Vascular Smooth Muscle Cells
Issue Date: 2018
Source: 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
Series/Report no.: Atherosclerosis
Abstract: 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.
URI: https://hdl.handle.net/10356/104138
http://hdl.handle.net/10220/47805
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2018.01.024
Rights: © 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/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCSE Journal Articles

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