{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:03:49Z","timestamp":1784610229854,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether circulating soluble Flt\u22121 (sFlt\u22121) and soluble Tie\u22122 (sTie\u22122) are associated with intraplaque neovascularization (IPN) in human carotid atherosclerotic plaques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty\u2212four patients with \u226550% carotid stenosis underwent conventional carotid ultrasound and superb microvascular imaging (SMI); 29 had plasma collected and 11 provided carotid endarterectomy specimens for histology. IPN was quantified as neovessel counts in 2\u2212minute SMI cine loops and as microvessel counts in excised plaques. Plasma VEGF\u2212A\/B\/C\/D, Ang\u22122, sFlt\u22121, and sTie\u22122 were measured by immunoassays. Public single\u2212cell RNA\u2212seq data from human carotid plaques were interrogated to map FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 expression to specific plaque cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IPN was detected in 33\/44 (75%) patients, with 0\u201316 neovessels on SMI (median 4). Plasma sFlt\u22121 correlated with SMI neovessel counts (r=0.42, p=0.030), with a similar trend for sTie\u22122 (r=0.37, p=0.057), whereas VEGF\u2212A\/B\/C\/D and Ang\u22122 showed no significant relationships. In the surgical subgroup, histological neovessel counts correlated with sFlt\u22121 (r=0.65, p=0.030) and SMI neovessel count (\n                      <jats:italic>r= 0.68, p =0.02)<\/jats:italic>\n                      but not sTie\u22122. sFlt\u22121 and sTie\u22122 correlated with BMI (and sTie\u22122 also with age), yet log\u2212sFlt\u22121 remained independently associated with SMI\u2212derived neovessel counts after adjustment for age and BMI (B\u00a0=\u00a013.24, 95% CI 0.17\u201326.30, p=0.047; R\u00b2=0.18), while sTie\u22122 was not. No significant associations were observed between IPN or sFlt\u22121\/sTie\u22122 and lipid profile, CRP, leukocyte counts, or other conventional risk factors. Single\u2212cell transcriptomics showed FLT1 and ANGPT2 broadly expressed across endothelial, smooth\u2212muscle, and myeloid clusters, with TEK largely confined to endothelial cells and ANGPT1 to smooth\u2212muscle cells, supporting local activation of VEGF\u2013FLT1 and Ang\u2013TEK\/Tie\u22122 signaling within plaques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this pilot study, higher plasma sFlt\u22121, and, to a lesser degree sTie\u22122, correlated with carotid IPN on SMI and histology, independent of age and BMI. These findings suggest that soluble VEGF\u2212 and Ang\/Tie\u22122\u2013receptor pathways may serve as circulating, context\u2212sensitive markers of intraplaque angiogenesis and plaque vulnerability, meriting evaluation in larger longitudinal cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1791571","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:20:28Z","timestamp":1784607628000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma levels of soluble Flt-1 and Tie-2 correlate with neovascularization in human carotid atherosclerotic plaques \u2013 a pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Mahtab","family":"Zamani","sequence":"first","affiliation":[{"name":"Department of Neurology, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, 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B.","family":"Dahl","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika Elisabeth","family":"Michelsen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]},{"name":"Research Institute of Internal Medicine, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Ueland","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]},{"name":"Research Institute of Internal Medicine, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Thrombosis Research Center, Division of Internal Medicine, University Hospital of North Norway","place":["Troms\u00f8, 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