Circulating Myeloperoxidase (MPO)-DNA complexes as marker for Neutrophil Extracellular Traps (NETs) levels and the association with cardiovascular risk factors in the general population

PLoS One. 2021 Aug 11;16(8):e0253698. doi: 10.1371/journal.pone.0253698. eCollection 2021.

Abstract

Introduction: Neutrophil extracellular traps (NETs) are DNA scaffolds enriched with antimicrobial proteins. NETs have been implicated in the development of various diseases, such as cardiovascular disease. Here, we investigate the association of demographic and cardiovascular (CVD) risk factors with NETs in the general population.

Material and methods: Citrated plasma was collected from 6449 participants, aged ≥55 years, as part of the prospective population-based Rotterdam Study. NETs were quantified by measuring MPO-DNA complex using an ELISA. We used linear regression to determine the associations between MPO-DNA complex and age, sex, cardio-metabolic risk factors, and plasma markers of inflammation and coagulation.

Results: MPO-DNA complex levels were weakly associated with age (log difference per 10 year increase: -0.04 mAU/mL, 95% confidence interval [CI] -0.06;-0.02), a history of coronary heart disease (yes versus no: -0.10 mAU/mL, 95% CI -0.17;-0.03), the use of lipid-lowering drugs (yes versus no: -0.06 mAU/mL, 95% CI -0.12;-0.01), and HDL-cholesterol (per mmol/l increase: -0.07 mAU/mL/, 95% CI -0.12;-0.03).

Conclusions: Older age, a history of coronary heart disease, the use of lipid-lowering drugs and higher HDL-cholesterol are weakly correlated with lower plasma levels of NETs. These findings show that the effect of CVD risk factors on NETs levels in a general population is only small and may not be of clinical relevance. This supports that NETs may play a more important role in an acute phase of disease than in a steady state situation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / metabolism
  • DNA / blood*
  • DNA / metabolism
  • Extracellular Traps / metabolism*
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Middle Aged
  • Peroxidase / blood*
  • Peroxidase / metabolism
  • Prospective Studies

Substances

  • DNA
  • MPO protein, human
  • Peroxidase

Grants and funding

The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; The Netherlands Organisation for Scientific Research (NWO); The Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); The Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. We acknowledge the support of the Netherlands Cardiovascular Research Initiative which is supported by the Dutch Heart Foundation (CVON2015-01: CONTRAST), the support of the Brain Foundation Netherlands (HA2015.01.06), and the support of Health~Holland, Top Sector Life Sciences & Health (LSHM17016), Medtronic and Cerenovus. The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. The measurement of MPO-DNA complex levels in participants of the Rotterdam study was supported by a research grant (Prof. Heimburger Award 2018, CSL Behring). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.