Glycophorin C in carotid atherosclerotic plaque reflects intraplaque hemorrhage and pre-procedural neurological symptoms.
This readme accompanies the paper "Glycophorin C in carotid atherosclerotic plaque reflects intraplaque hemorrhage and pre-procedural neurological symptoms." by J.M. Mekke et al. medRxiv 2021.
Introduction The accumulation of erythrocyte membranes within an atherosclerotic plaque may contribute to the deposition of free cholesterol and thereby the enlargement of the necrotic core. Erythrocyte membranes can be visualized and quantified in the plaque by immunostaining for the erythrocyte marker glycophorin C. Consequently, we hypothesized, that the accumulation of erythrocytes quantified by glycophorin C is a marker for plaque vulnerability and may therefore reflect intraplaque hemorrhage (IPH), vulnerability of plaques and predict pre-procedural neurological symptoms.
Methods We visualized and quantified glycophorin C, defined as the total plaque area that is positive for glycophorin C, in single slides of culprit lesions of human atherosclerotic plaque samples, from 1,819 consecutive asymptomatic and symptomatic patients undergoing carotid endarterectomy from the Athero-Express Biobank with the slideToolKit method. Lipid core, calcifications, collagen content, SMC content and macrophage burden were using a semi-quantitative scoring method, which was dichotomized for as no/minor or moderate/heavy staining according to predefined criteria. IPH was scored as either present or not present.
Results The prevalence of IPH and pre-procedural neurological symptoms were 62.4% and 87.1%, respectively. The amount of glycophorin staining was significantly higher in samples from men compared to samples of women (median 7.15 (IQR:3.37, 13.41) versus median 4.06 (IQR:1.98, 8.32), p<0.001). Glycophorin C was associated with IPH adjusted for clinical confounders(OR 1.90; 95% CI 1.63, 2.21; p=<0.001). Glycophorin C was significantly associated with ipsilateral pre-procedural neurological symptoms (OR:1.27, 95%CI:1.06-1.41, p=0.005).Sex-stratified analysis, showed that this was also the case for men (OR 1.37; 95%CI 1.12, 1.69; p=0.003), but not for women (OR 1.15; 95%CI 0.77, 1.73; p=0.27). Glycophorin C was associated with classical features of a vulnerable plaque, such as a larger lipid core, a higher macrophage burden, less calcifications, a lower collagen and SMC content. There were marked sex differences, in men, glycophorin C was associated with calcifications and collagen while these associations were not found in women.
Conclusion The accumulation of erythrocytes in atherosclerotic plaque quantified and visualized byglycophorin C was independently associated with the presence of IPH, symptomatic preprocedural symptoms in men, and with a more vulnerable plaque composition in both men and women. This strengthens the notion that the accumulation of erythrocytes quantified by glycophorin C can be used as a marker for plaque vulnerability.
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Figure: Study design and flowchart of study participants A. Graphical illustration of the study design. Created with BioRender.com{target="_blank"}. B. Number of individuals included in the current study.
Data as shared through DataverseNL.
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Dr. Sander W. van der Laan is funded through EU H2020 TO_AITION (grant number: 848146), EU HORIZON NextGen (grant number: 101136962), EU HORIZON MIRACLE (grant number: 101115381), and HealthHolland PPP Allowance ‘Getting the Perfect Image’.
We are thankful for the support of the Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation (CVON 2011/B019 and CVON 2017-20: Generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS I&II]), the ERA-CVD program ‘druggable-MI-targets’ (grant number: 01KL1802), and the Leducq Fondation ‘PlaqOmics’. The research for this contribution was made possible by the AI for Health working group of the EWUU alliance (https://aiforhealth.ewuu.nl/).
Plaque samples are derived from carotid endarterectomies as part of the Athero-Express Biobank Study which is an ongoing study in the UMC Utrecht.
Dr. Sander W. van der Laan has received Roche funding for unrelated work.
_Version:_ v1.1</br>
_Last update:_ 2023-09-12</br>
_Written by:_ Joost M. Mekke | Sander W. van der Laan (s.w.vanderlaan [at] gmail [dot] com).
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**Changes log**
* v1.1.0 Added WORCS. Added images. Added main figure.
* v1.0.0 Initial version.
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