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Functional pathways associated with human carotid atheroma: a proteomics analysis

Hypertension Research volume 42, pages 362–373 (2019)Cite this article

Abstract

Advances in large-scale analysis are becoming very useful in understanding health and disease. Here, we used high-throughput mass spectrometry to identify differentially expressed proteins between early and advanced lesions. Carotid endarterectomy samples were collected and dissected into early and advanced atherosclerotic lesion portions. Proteins were extracted and subjected to liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Differentially expressed proteins were identified and verified using multiple reaction monitoring (MRM), on which advanced systems biology and enrichment analyses were performed. The identified proteins were further compared to the transcriptomic data of 32 paired samples obtained from early and advanced atherosclerotic lesions. A total of 95 proteins were upregulated, and 117 proteins were downregulated in advanced lesions compared to early atherosclerotic lesions (p < 0.05). The upregulated proteins were associated with proatherogenic processes, whereas downregulated proteins were involved in extracellular matrix organization and vascular smooth muscle cytoskeleton. Many of the identified proteins were linked to various “upstream regulators”, among which TGFβ had the highest connections. Specifically, a total of 19 genes were commonly upregulated, and 30 genes were downregulated at the mRNA and protein levels. These genes were involved in vascular smooth muscle cell activity, for which enriched transcription factors were identified. This study deciphers altered pathways in atherosclerosis and identifies upstream regulators that could be candidate targets for treatment.

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Funding

A.N. was awarded a scholarship from “La Nouvelle Société Francophone d’Athérosclérose” (NSFA). This work was supported by a Campus France grant from “Coopération pour l’Évaluation et le Développement de la Recherche” (CEDRE).

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  1. These authors contributed equally: Ali Nehme, Firas Kobeissy

Authors and Affiliations

  1. EA4173, Functional genomics of arterial hypertension, UCBL-1, Villeurbanne, France

    Ali Nehme

  2. PRASE, DSST, Lebanese University, Beirut, Lebanon

    Ali Nehme & Kazem Zibara

  3. Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    Firas Kobeissy

  4. Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, USA

    Jingfu Zhao, Rui Zhu & Yehia Mechref

  5. Service de Chirurgie Vasculaire, Hôpital Universitaire E Herriot, Lyon, 69008, France

    Patrick Feugier

  6. Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon

    Kazem Zibara

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Nehme, A., Kobeissy, F., Zhao, J. et al. Functional pathways associated with human carotid atheroma: a proteomics analysis. Hypertens Res 42, 362–373 (2019). https://doi.org/10.1038/s41440-018-0192-4

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  • DOI: https://doi.org/10.1038/s41440-018-0192-4

Keywords

  • Atherosclerosis
  • Carotid artery
  • Proteome
  • Transcriptome
  • Transcription regulators

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