Transcriptomic and Proteomic Profiling of Human Stable and Unstable Carotid Atherosclerotic Plaques - PubMed (original) (raw)

Transcriptomic and Proteomic Profiling of Human Stable and Unstable Carotid Atherosclerotic Plaques

Mei-Hua Bao et al. Front Genet. 2021.

Abstract

Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by _cis_-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.

Keywords: RNA-seq; atherosclerosis; proteome; transcriptome; unstable plaques.

Copyright © 2021 Bao, Zhang, Huang, Zhou, Guo, Xu and Liu.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1

FIGURE 1

The hierarchical clustering heatmap of 20 DE mRNAs, lncRNAs, circRNAs, and proteins. A–D: The hierarchical clustering heatmap of mRNAs (A), lncRNAs (B), circRNA (C), proteins (D). (E): The heatmap of overlapping genes between current study and GSE41571; (F): the qPCR verification of 6 randomly selected upregulated mRNAs, lncRNAs, and circRNAs. (G): the qPCR verification of 6 randomly selected downregulated mRNAs, lncRNAs, and circRNAs. The values (mean ± S.D. from 5 independent experiments) are relative to Stable group, which was set as 1. *p < 0.05, **p < 0.01. Red box: the overlapping genes between current study (A) and GSE41571 (E).

FIGURE 2

FIGURE 2

The protein-protein interactions of DEPs and the clusters identified by MCODE. Red box: cluster1; Green box: cluster 2; Yellow box: cluster 3; Pink box: cluster 4.

FIGURE 3

FIGURE 3

The lncRNA (or circRNA)-miRNA-mRNA interactions network. Yellow diamond: lncRNA or circRNA; green circle: miRNA; blue square: mRNA.

References

    1. Bai H.-L., Lu Z.-F., Zhao J.-J., Ma X., Li X.-H., Xu H., et al. (2019). Microarray Profiling Analysis and Validation of Novel Long Noncoding RNAs and mRNAs as Potential Biomarkers and Their Functions in Atherosclerosis. Physiol. Genomics 51, 644–656. 10.1152/physiolgenomics.00077.2019 - DOI - PMC - PubMed
    1. Cao Q., Guo Z., Du S., Ling H., Song C. (2020). Circular RNAs in the Pathogenesis of Atherosclerosis. Life Sci. 255, 117837. 10.1016/j.lfs.2020.117837 - DOI - PubMed
    1. Çekin N., Özcan A., Göksel S., Arslan S., Pınarbaşı E., Berkan Ö. (2018). Decreased FENDRR and LincRNA-P21 Expression in Atherosclerotic Plaque. Anatol J. Cardiol. 19, 131–136. 10.14744/AnatolJCardiol.2017.8081 - DOI - PMC - PubMed
    1. Farokhzadian J., Mangolian Shahrbabaki P., Bagheri V. (2019). S100A12-CD36 axis: A Novel Player in the Pathogenesis of Atherosclerosis. Cytokine 122, 154104. 10.1016/j.cyto.2017.07.010 - DOI - PubMed
    1. Fasolo F., Di Gregoli K., Maegdefessel L., Johnson J. L. (2019). Non-coding RNAs in Cardiovascular Cell Biology and Atherosclerosis. Cardiovasc. Res. 115, 1732–1756. 10.1093/cvr/cvz203 - DOI - PMC - PubMed

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