Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke

Nirmal Vadgama, Douglas Lamont, John Hardy, Jamal Nasir, Ruth C. Lovering

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Stroke is a common disorder with significant morbidity and mortality, and complex aetiology involving both environmental and genetic risk factors. Although some of the major risk factors for stoke, such as smoking and hypertension, are well-documented, the underlying genetic and detailed molecular mechanisms remain elusive. Exploring the relevant biochemical pathways may contribute to the clinical diagnosis of stroke and shed light on its aetiology. A comparative proteomic analysis of blood serum of a pair of monozygotic (MZ) twins discordant for ischaemic stroke (IS) was performed using a label-free quantitative proteomics approach. To overcome the limit of reproducibility in the serum preparation, two separate runs were performed, each consisting of three technical replicates per sample. Biological processes associated with proteins differentially expressed between the twins were explored with gene ontology (GO) classification using the functional analysis tool g:Profiler. ANOVA test performed in Progenesis LC-MS identified 179 (run 1) and 209 (run 2) proteins as differentially expressed between the affected and unaffected twin (p < 0.05). Furthermore, the level of serum fibulin 1, an extracellular matrix protein associated with arterial stiffness, was on average 13.37-fold higher in the affected twin. Each dataset was then analysed independently, and the proteins were classified according to GO terms. The categories overrepresented in the affected twin predominantly corresponded to stroke-relevant processes, including wound healing, blood coagulation and haemostasis, with a high proportion of the proteins overexpressed in the affected twin associated with these terms. By contrast, in the unaffected twin diagnosed with atopic dermatitis, there were increased levels of keratin proteins and GO terms associated with skin development. The identification of cellular pathways enriched in IS as well as the upregulation of fibulin 1 sheds new light on the underlying disease-causing mechanisms at the molecular level. Our findings of distinct proteomic signatures associated with IS and atopic dermatitis suggest proteomic profiling could be used as a general approach for improved diagnostic, prognostic and therapeutic strategies.

    Original languageEnglish
    Pages (from-to)157-165
    Number of pages9
    JournalMolecular and Cellular Biochemistry
    Volume456
    Issue number1-2
    Early online date29 Jan 2019
    DOIs
    Publication statusPublished - 15 Jun 2019

    Fingerprint

    Monozygotic Twins
    Proteomics
    Stroke
    Gene Ontology
    Atopic Dermatitis
    Proteins
    Serum
    Biological Phenomena
    Vascular Stiffness
    Extracellular Matrix Proteins
    Blood Coagulation
    Keratins
    Hemostasis
    Wound Healing
    Molecular Biology
    Analysis of Variance
    Up-Regulation
    Smoking
    Hypertension
    Morbidity

    Keywords

    • Biomarker
    • Fibulin 1
    • Gene
    • Monozygotic twins
    • Proteomics
    • Stroke

    Cite this

    Vadgama, Nirmal ; Lamont, Douglas ; Hardy, John ; Nasir, Jamal ; Lovering, Ruth C. / Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke. In: Molecular and Cellular Biochemistry. 2019 ; Vol. 456, No. 1-2. pp. 157-165.
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    Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke. / Vadgama, Nirmal; Lamont, Douglas; Hardy, John; Nasir, Jamal; Lovering, Ruth C.

    In: Molecular and Cellular Biochemistry, Vol. 456, No. 1-2, 15.06.2019, p. 157-165.

    Research output: Contribution to journalArticleResearchpeer-review

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