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Increasing blood pressure predicts levels of circulating neutrophil extracellular traps in untreated hypertensive patients

Hypertension Research volume 48, pages 2688–2700 (2025)Cite this article

Abstract

Neutrophil extracellular traps (NETs) are increasingly implicated in the pathophysiology of cardiovascular disease; however, data regarding their clinical significance in hypertension-mediated vascular damage is scarce. We recruited untreated, newly diagnosed patients with essential hypertension (UHTs) and age- and sex- matched healthy, normotensive controls (NTs). Ambulatory blood pressure (BP) monitoring was performed with the Mobil-O-Graph-NG device. NET-specific myeloperoxidase (MPO)-DNA complexes were measured in plasma with ELISA. Carotid pulse wave velocity (PWV) was calculated by using a high-definition echo-tracking system. Skin microcirculation was assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. A total of 139 participants of whom 99 UHTs (mean age 48.9 ± 8.34 years) and 40 NTs (mean age 47.4 ± 7.38 years) were included in the study. Using categorical regression with optimal scaling, various peripheral and central BP parameters were significantly associated with MPO-DNA complexes levels; 24 h peripheral systolic BP (p < 0.001) was the strongest predictor of hypertension-related NETosis, after adjusting for potential confounders. MPO-DNA complexes levels were positively associated with mean carotid PWV (p = 0.033) and baseline flux (p = 0.017) and negatively associated with baseline to peak flux (p = 0.020) and cutaneous vascular conductance increase (p = 0.034). In multivariate analysis, carotid PWV showed an independent association with MPO-DNA complexes. Circulating NETs levels are tightly associated with BP. Of note, the 24 h peripheral SBP load is the strongest predictor of NETs burden. Moreover, NETs are strongly related to surrogate measures of micro- and macrovascular damage, suggesting their potential role as a diagnostic and/or therapeutic target in hypertension.

MPO-DNA levels are strongly associated with peripheral and central BP parameters in untreated hypertensives, with 24h peripheral SBP being the strongest predictor of circulating NETs burden. MPO-DNA levels are correlated with surrogate markers of micro- and macrovascular damage. MPO-DNA levels are independently associated with carotid artery stiffness.

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Acknowledgements

Part of this work was funded by the Hellenic Society of Hypertension and Greek General Secretariat for Research and Innovation (GSRI), Regional Excellence Programme InTechThrace, grant MIS-5047285.

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  1. These authors contributed equally: A. Malliora, A. Lazaridis

Authors and Affiliations

  1. Third Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    A. Malliora, A. Lazaridis, V. Kotsis & E. Gkaliagkousi

  2. First Department of Internal Medicine and Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece

    A.-M. Natsi, V. Papadopoulos, C. Antoniadou, E. Gavriilidis, D. Tsilingiris & P. Skendros

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Correspondence to E. Gkaliagkousi.

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Malliora, A., Lazaridis, A., Natsi, AM. et al. Increasing blood pressure predicts levels of circulating neutrophil extracellular traps in untreated hypertensive patients. Hypertens Res 48, 2688–2700 (2025). https://doi.org/10.1038/s41440-025-02306-9

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