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

Federico Carbone; Edoardo Elia; Matteo Casula; Aldo Bonaventura; Maria Bertolotto; Silvia Minetti; Nathan Artom; Giovanni G Camici; Paola Contini; Roberto Pontremoli; Francesca Viazzi; Stefano Bertolini; Aldo Pende; Livia Pisciotta; Fabrizio Montecucco; Luca Liberale

doi:10.1016/j.numecd.2022.10.014

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

Nutr Metab Cardiovasc Dis. 2023 Jan;33(1):185-193. doi: 10.1016/j.numecd.2022.10.014. Epub 2022 Oct 31.

Authors

Federico Carbone¹, Edoardo Elia², Matteo Casula², Aldo Bonaventura³, Maria Bertolotto², Silvia Minetti², Nathan Artom⁴, Giovanni G Camici⁵, Paola Contini⁶, Roberto Pontremoli⁶, Francesca Viazzi⁶, Stefano Bertolini⁷, Aldo Pende⁶, Livia Pisciotta⁶, Fabrizio Montecucco⁸, Luca Liberale⁹

Affiliations

¹ 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.
² First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
³ Medicina Generale 1, Medical Center, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, Varese, Italy.
⁴ Department of Internal Medicine, Ospedale S. Paolo di Savona, 30 via Genova, 17110 Savona, Italy.
⁵ Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland.
⁶ 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.
⁷ Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.
⁸ 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.
⁹ 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. Electronic address: luca.liberale@unige.it.

PMID: 36411219
DOI: 10.1016/j.numecd.2022.10.014

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: Inflammation; Matrix-metalloproteinases; Metabolic syndrome; Myeloperoxidase; Neutrophil.

Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Humans
Inflammation
Matrix Metalloproteinase 8
Matrix Metalloproteinase 9
Metabolic Syndrome* / diagnosis
Neutrophils / metabolism
ROC Curve
Waist Circumference

Substances

Matrix Metalloproteinase 8
Matrix Metalloproteinase 9
Biomarkers