{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:37:02Z","timestamp":1786703822150,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"publisher","award":["202208500038"],"award-info":[{"award-number":["202208500038"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["01-003-2022-0417"],"award-info":[{"award-number":["01-003-2022-0417"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["18CDV-02"],"award-info":[{"award-number":["18CDV-02"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU H2020","award":["848146"],"award-info":[{"award-number":["848146"]}]},{"name":"EU HORIZON NextGen","award":["101136962"],"award-info":[{"award-number":["101136962"]}]},{"name":"EU HORIZON MIRACLE","award":["101115381"],"award-info":[{"award-number":["101115381"]}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016036","name":"Health\u223cHolland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016036","name":"Top Sector Life Sciences & Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In patients with atherosclerotic internal carotid artery stenosis, the risk of subsequent ischaemic stroke is higher in those presenting with a cerebral transient ischaemic attack (TIA) than in those with amaurosis fugax (AFX; transient monocular blindness). While AFX is associated with more stable histological characteristics, the underlying molecular mechanisms remain unclear. We hypothesized that biological processes and gene expression profiles in carotid plaques of patients with AFX differ from those with cerebral TIA and stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We analysed carotid plaques from 2508 patients undergoing endarterectomy between 2002 and 2022. Bulk RNA sequencing (RNA-seq) was performed on 1088 plaques (136 asymptomatic, 179 AFX, 481 TIA, 292 stroke). Single-cell RNA-seq from 46 previously profiled plaques was used to identify cell-specific transcriptomic signatures. Mass spectrometry-based proteomics (n = 189) and targeted plasma proteomics (n = 1291) were used to validate the molecular differences. AFX plaques showed fewer lipid-rich cores than those from cerebral TIA [odds ratio (95% CI): 1.41 (1.03\u20131.94)] or stroke [1.42 (1.01\u20131.99)]. RNA-seq identified 408 differentially expressed genes (DEGs) between AFX and TIA and 463 between AFX and stroke (FDR &amp;lt; 0.1), while AFX and asymptomatic plaques showed only 10 DEGs. AFX plaques were enriched for vascular smooth muscle cell signatures and extracellular matrix remodelling, while cerebral TIA and stroke plaques exhibited macrophage-driven inflammatory molecular signatures. These transcriptomic differences were confirmed by plaque proteomic analyses. In parallel, circulating proteomic profiling revealed higher levels of inflammatory and thrombo-inflammatory markers in cerebral TIA and stroke compared with AFX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AFX plaques exhibit stable, SMC-dominant molecular signatures that differ markedly from the macrophage-driven inflammatory profiles of cerebral TIA and stroke plaques. These findings support AFX as a biologically distinct entity with potential implications for risk stratification and personalized treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag116","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:49:46Z","timestamp":1780055386000},"page":"1443-1454","source":"Crossref","is-referenced-by-count":0,"title":["Gene expression profiles of carotid plaques differ between patients with amaurosis fugax and those with cerebral transient ischaemic attack or stroke"],"prefix":"10.1093","volume":"122","author":[{"given":"Tian","family":"Lan","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor B H","family":"van der Zalm","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylin C A","family":"Palm","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Diez Benavente","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander W","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Department of Genome Sciences, University of Virginia, 1335 Lee Street, West Complex, Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique P V","family":"de Kleijn","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Medical Centre Utrecht , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-2989","authenticated-orcid":false,"given":"Ynte M","family":"Ruigrok","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-5179","authenticated-orcid":false,"given":"Joost A","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Medical Centre Utrecht , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert J","family":"de Borst","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Medical Centre Utrecht , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Board of Directors, Reinier de Graaf Gasthuis, Reinier de Graafweg 5, 2625 AD Delft, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Bart van der Worp","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-387X","authenticated-orcid":false,"given":"Martin","family":"Dichgans","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital LMU, Feodor-Lynen-Stra\u00dfe 17, Munich 81377 ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy), Institute for Stroke and Dementia Research (ISD), Feodor-Lynen-Stra\u00dfe 17, Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, Institute for Stroke and Dementia Research (ISD), Feodor-Lynen-Stra\u00dfe 17, Munich 81377 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Pettenkoferstra\u00dfe 8a\/9, Munich 81377 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