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Among biomarkers of neutrophil activity, matrix metalloproteinases 8 independently predicts remission of metabolic syndrome

  • Federico Carbone
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
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  • Edoardo Elia
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Matteo Casula
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Aldo Bonaventura
    Affiliations
    Medicina Generale 1, Medical Center, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, Varese, Italy
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  • Maria Bertolotto
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Silvia Minetti
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Nathan Artom
    Affiliations
    Department of Internal Medicine, Ospedale S. Paolo di Savona, 30 via Genova, 17110 Savona, Italy
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  • Giovanni G. Camici
    Affiliations
    Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland
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  • Paola Contini
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132 Genoa, Italy
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  • Roberto Pontremoli
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132 Genoa, Italy
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  • Francesca Viazzi
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132 Genoa, Italy
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  • Stefano Bertolini
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Aldo Pende
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132 Genoa, Italy
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  • Livia Pisciotta
    Affiliations
    Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132 Genoa, Italy
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  • Author Footnotes
    1 Those authors equally contributed to this work.
    Fabrizio Montecucco
    Footnotes
    1 Those authors equally contributed to this work.
    Affiliations
    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy

    First Clinic of Internal Medicine, Department of Internal Medicine, and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
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  • Author Footnotes
    1 Those authors equally contributed to this work.
    Luca Liberale
    Correspondence
    Corresponding author. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy. Address: 6 viale Benedetto XV, 16132 Genoa, Italy. Fax: +39 010 353 86 86.
    Footnotes
    1 Those authors equally contributed to this work.
    Affiliations
    First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy

    IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
    Search for articles by this author
  • Author Footnotes
    1 Those authors equally contributed to this work.
Published:October 31, 2022DOI:https://doi.org/10.1016/j.numecd.2022.10.014

      Highlights

      • Low grade chronic inflammation plays an important role in metabolic syndrome (i.e. metaflammation).
      • Neutrophils are pivotal cells for the onset and propagation of metaflammation.
      • Neutrophil biomarkers MMP8, MMP-9 and MPO correlate with metabolic syndrome severity.
      • Anti-inflammatory neutrophil mediators such as TIMPs do not correlate with disease severity.
      • Lower levels of MMP8 at baseline independently predict an improvement of metabolic syndrome.

      Abstract

      Background and aims

      Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements.

      Methods and Results

      patients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961–0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949–0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings.

      Conclusion

      Improvement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.

      Keywords

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