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.

Approach:

• Study Population: Forty-four patients with ≥50% carotid stenosis underwent carotid ultrasound and superb microvascular imaging (SMI); plasma was collected from 29 patients and carotid endarterectomy specimens were obtained from 11 for histology.
• Measurement Techniques: IPN was quantified using SMI and histological analysis, while plasma levels of VEGF−A/B/C/D, Ang−2, sFlt−1, and sTie−2 were measured by immunoassays.
• Data Analysis: Single-cell RNA-seq data from human carotid plaques were analyzed to map expression of FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 to specific plaque cell populations.

Key Findings:

• IPN was detected in 33 out of 44 (75%) patients, with a median of 4 neovessels (range 0–16).
• Plasma sFlt−1 correlated with SMI neovessel counts (r=0.42, p=0.030), and sTie−2 showed a trend towards correlation (r=0.37, p=0.057).
• In the surgical subgroup, histological neovessel counts correlated with sFlt−1 (r=0.65, p=0.030) and SMI neovessel count (r=0.68, p=0.02).
• Log-sFlt−1 remained independently associated with SMI-derived neovessel counts after adjustment for age and BMI (B = 13.24, p=0.047).
• No significant associations were found between IPN or sFlt−1/sTie−2 and conventional risk factors.

Interpretation:

Limitations:

• The small sample size limits the generalizability of the findings.
• The cross-sectional design does not establish causality.

Conclusion: