Preliminary Observations of Spatial Imbalance between Lymphangiogenesis and Angiogenesis within Carotid...

Atherosclerotic plaque progression involves dynamic interactions between angiogenesis and lymphangiogenesis. This pilot, hypothesis-generating study aimed to explore the spatial balance between blood microvessels and lymphatic vessels in human carotid plaques.

Carotid plaques from 4 patients who underwent carotid endarterectomy were examined histologically. Blood microvessels (CD31+) and lymphatic vessels (Podoplanin+) were quantified in severely and mildly thickened lesions. The blood microvessel-to-lymphatic vessel (BMV/LV) ratio was compared between regions, along with macrophage polarization (CD80+: M1 and CD163+: M2).

Severely thickened lesions exhibited a 15.5-fold higher density of blood microvessels than mildly thickened lesions (median 31 vs. 2 vessels; p = 0.012), whereas lymphatic vessel counts were comparable (median 31 vs. 32 vessels; p = 0.978). Consequently, the BMV/LV ratio was 16-fold higher in severely thickened lesions (1.203 vs. 0.121, p = 0.060). CD80-positive areas were larger in severely thickened lesions (0.395% vs. 0.078% area, p = 0.006), whereas CD163-positive areas were comparable between regions (1.036% vs. 0.215%, p = 0.154).

Mildly thickened carotid atherosclerotic plaques demonstrated relative lymphatic predominance, whereas severely thickened lesions showed angiogenic predominance accompanied by increased M1 macrophage infiltration. These exploratory findings suggest that regional imbalance between lymphatic vessels and blood microvessels within individual plaques may contribute to localized plaque vulnerability.