{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:24Z","timestamp":1787027844748,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2013T084"],"award-info":[{"award-number":["2013T084"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2013T083"],"award-info":[{"award-number":["2013T083"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Introduction: Preeclampsia (PE) represents a hypertensive pregnancy disorder that is associated with increased cardiovascular disease (CVD) risk. This increased risk has been attributed to accelerated atherosclerosis, with inflammation being a major contributor. Neutrophils play an important role in the onset and progression of atherosclerosis and have been associated with vascular damage in the placenta as well as the chronic inflammatory state in women with PE. We therefore investigated whether circulating neutrophil numbers or reactivity were associated with the presence and severity of subclinical atherosclerosis in women with a history of PE. Methods: Women aged 45\u201360 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery &lt;34 weeks of gestation) (n = 90), but without symptomatic CVD burden were screened for the presence of subclinical coronary artery disease (CAD) using both contrast-enhanced and non-contrast coronary CT angiography. Subclinical CAD was defined as a coronary artery calcium (CAC) score \u2265100 Agatston Units and\/or \u226550% coronary luminal stenosis. We assessed whether the numbers and activity of circulating neutrophils were associated with the presence of subclinical CAD and as secondary outcome measurements, with the presence of any calcium (CAC score &gt; 0 AU) or stenosis, categorized as absent (0%), minimal to mild (&gt;0 and &lt;50%), and moderate to severe (\u226550%) narrowing of the coronary artery. Blood was drawn just before CT and neutrophil numbers were assessed by flow cytometry. In addition, the presence of the chemokine receptors CXCR2 and CXCR4, which are known to be instrumental in neutrophil recruitment, and neutrophil activity upon stimulation with the bacterial peptide N-Formylmethionyl-leucyl-phenylalanine (fMLF) was assessed by flow cytometry. Results: Of the participating women, with an average age of 49 years, 13% (12 out of 90) presented with subclinical signs of CAD (CAC score \u2265100 AU and\/or \u226550% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (&gt;0). Total white blood cell count and neutrophil counts were not associated with the presence of subclinical CAD or with a positive CAC score. When assessing the presence of the chemokine receptors CXCR4 and CXCR2, we observed a slight decrease of neutrophil CXCR2 expression in women with CAC (median MFI 22.0 [interquartile range (IQR) 20.2\u201323.8]) compared to women without CAC (23.8 [IQR 21.6\u201325.6], p = 0.02). We observed no differences regarding neutrophil CXCR4 expression. In addition, expression of the early activity marker CD35 was slightly lower on neutrophils of women with subclinical CAD (median MFI 1.6 [IQR 1.5\u20131.9] compared to 1.9 [IQR 1.7\u20132.1] in women without CAD, p = 0.02). However, for all findings, statistical significance disappeared after adjustment for multiple testing. Conclusion: Our findings indicate that neutrophil counts and (re)activity are not directly associated with silent CAD disease burden and as such are not suitable as biomarkers to predict the presence of subclinical CAD in a high-risk population of women with a history of preeclampsia.<\/jats:p>","DOI":"10.3390\/cells9020468","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T04:21:26Z","timestamp":1582604486000},"page":"468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia"],"prefix":"10.3390","volume":"9","author":[{"given":"John A.L.","family":"Meeuwsen","sequence":"first","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"de Vries","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerbrand A.","family":"Zoet","sequence":"additional","affiliation":[{"name":"Wilhelmina Children\u2019s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Franx","sequence":"additional","affiliation":[{"name":"Wilhelmina Children\u2019s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart C. J. M.","family":"Fauser","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela H. E. M.","family":"Maas","sequence":"additional","affiliation":[{"name":"Department cardiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta K.","family":"Velthuis","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolande E.","family":"Appelman","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centre, VU Medical Centre, VU University, 1081 VV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank L.","family":"Visseren","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imo E.","family":"Hoefer","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-3825","authenticated-orcid":false,"given":"Bas B.","family":"van Rijn","sequence":"additional","affiliation":[{"name":"Wilhelmina Children\u2019s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester M.","family":"den Ruijter","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-0066","authenticated-orcid":false,"given":"Saskia C.A.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Center Translational Immunology, University Medical Center Utrecht, Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","unstructured":"Mendis, S., Armstrong, T., Bettcher, D., Branca, F., Lauer, J., Mace, C., Poznyak, V., Riley, L., Da Costa E Silva, V., and Stevens, G. 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