ArticleFrontiers in immunology2026
Plasma levels of soluble Flt-1 and Tie-2 correlate with neovascularization in human carotid atherosclerotic plaques - a pilot study.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To determine whether circulating soluble Flt-1 (sFlt-1) and soluble Tie-2 (sTie-2) are associated with intraplaque neovascularization (IPN) in human carotid atherosclerotic plaques. Methods: Forty-four patients with ≥50% 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-minute SMI cine loops and as microvessel counts in excised plaques. Plasma VEGF-A/B/C/D, Ang-2, sFlt-1, and sTie-2 were measured by immunoassays. Public single-cell RNA-seq data from human carotid plaques were interrogated to map FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 expression to specific plaque cell populations. Results: IPN was detected in 33/44 (75%) patients, with 0-16 neovessels on SMI (median 4). Plasma sFlt-1 correlated with SMI neovessel counts (r=0.42, p=0.030), with a similar trend for sTie-2 (r=0.37, p=0.057), whereas VEGF-A/B/C/D and Ang-2 showed no significant relationships. In the surgical subgroup, histological neovessel counts correlated with sFlt-1 (r=0.65, p=0.030) and SMI neovessel count ( Conclusion: In this pilot study, higher plasma sFlt-1, and, to a lesser degree sTie-2, correlated with carotid IPN on SMI and histology, independent of age and BMI. These findings suggest that soluble VEGF- and Ang/Tie-2-receptor pathways may serve as circulating, context-sensitive markers of intraplaque angiogenesis and plaque vulnerability, meriting evaluation in larger longitudinal cohorts.
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