Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia
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...
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MDPI AG
2020-02-01
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Online Access: | https://www.mdpi.com/2073-4409/9/2/468 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
John A.L. Meeuwsen Judith de Vries Gerbrand A. Zoet Arie Franx Bart C. J. M. Fauser Angela H. E. M. Maas Birgitta K. Velthuis Yolande E. Appelman Frank L. Visseren Gerard Pasterkamp Imo E. Hoefer Bas B. van Rijn Hester M. den Ruijter Saskia C.A. de Jager |
spellingShingle |
John A.L. Meeuwsen Judith de Vries Gerbrand A. Zoet Arie Franx Bart C. J. M. Fauser Angela H. E. M. Maas Birgitta K. Velthuis Yolande E. Appelman Frank L. Visseren Gerard Pasterkamp Imo E. Hoefer Bas B. van Rijn Hester M. den Ruijter Saskia C.A. de Jager Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia Cells coronary artery disease preeclampsia neutrophils women |
author_facet |
John A.L. Meeuwsen Judith de Vries Gerbrand A. Zoet Arie Franx Bart C. J. M. Fauser Angela H. E. M. Maas Birgitta K. Velthuis Yolande E. Appelman Frank L. Visseren Gerard Pasterkamp Imo E. Hoefer Bas B. van Rijn Hester M. den Ruijter Saskia C.A. de Jager |
author_sort |
John A.L. Meeuwsen |
title |
Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia |
title_short |
Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia |
title_full |
Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia |
title_fullStr |
Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia |
title_full_unstemmed |
Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former Preeclampsia |
title_sort |
circulating neutrophils do not predict subclinical coronary artery disease in women with former preeclampsia |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-02-01 |
description |
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 45−60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <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 ≥100 Agatston Units and/or ≥50% 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 > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) 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 ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>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) 20.2−23.8]) compared to women without CAC (23.8 [IQR 21.6−25.6], <i>p</i> = 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 1.5−1.9] compared to 1.9 [IQR 1.7−2.1] in women without CAD, <i>p</i> = 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. |
topic |
coronary artery disease preeclampsia neutrophils women |
url |
https://www.mdpi.com/2073-4409/9/2/468 |
work_keys_str_mv |
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doaj-cd95b6e9312c41a8a111b4b9b477af3f2020-11-25T02:03:34ZengMDPI AGCells2073-44092020-02-019246810.3390/cells9020468cells9020468Circulating Neutrophils Do Not Predict Subclinical Coronary Artery Disease in Women with Former PreeclampsiaJohn A.L. Meeuwsen0Judith de Vries1Gerbrand A. Zoet2Arie Franx3Bart C. J. M. Fauser4Angela H. E. M. Maas5Birgitta K. Velthuis6Yolande E. Appelman7Frank L. Visseren8Gerard Pasterkamp9Imo E. Hoefer10Bas B. van Rijn11Hester M. den Ruijter12Saskia C.A. de Jager13Laboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsLaboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsWilhelmina Children’s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsWilhelmina Children’s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment cardiology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Radiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsAmsterdam University Medical Centre, VU Medical Centre, VU University, 1081 VV Amsterdam, The NetherlandsDepartment of Vascular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsCentral Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, 3584 CX Utrecht, The NetherlandsCentral Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, 3584 CX Utrecht, The NetherlandsWilhelmina Children’s Hospital Birth Center, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsLaboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsLaboratory for Experimental Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsIntroduction: 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 45−60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <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 ≥100 Agatston Units and/or ≥50% 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 > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) 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 ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>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) 20.2−23.8]) compared to women without CAC (23.8 [IQR 21.6−25.6], <i>p</i> = 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 1.5−1.9] compared to 1.9 [IQR 1.7−2.1] in women without CAD, <i>p</i> = 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.https://www.mdpi.com/2073-4409/9/2/468coronary artery diseasepreeclampsianeutrophilswomen |