LYVE-1 expression in the endothelium of newly formed vessels of carotid atherosclerotic plaque

Introduction. The discovery of specific markers of lymphatic endothelium, including LYVE-1, has led to a much better understanding of the structure and function of the lymphatic system. It has been shown that lymphatic system regulates immune responses, reverse cholesterol transport, and inflammation in atherosclerosis. LYVE-1 plays an important role in activating the function of the lymphatic system and is also one of the first markers of lymphangiogenesis. There are few morphological studies of lymphatic vessels in atherosclerotic plaques, and the obtained data are contradictory.

The aim of the study was to characterize the LYVE-1 receptor expression in the endothelium of newly formed vessels in carotid atherosclerotic plaques and to evaluate its relationship with the plaque structure.

Materials and methods. 34 carotid atherosclerotic plaques obtained during carotid endarterectomies were investigated using histological and immunohistochemical techniques. The density of LYVE-1+ vessels per 1 cm2 of plaque, combined expression of LYVE-1 and CD34, proportion of atheromatosis and calcifications, as well as severity of dust-like calcification, haemorrhage, overall macrophage response (CD68+), and plaque infiltration by M2 macrophage (CD206+) were evaluated.

Results. LYVE-1+ vessels were detected in 32 carotid atherosclerotic plaques, with a range of 5.7–1698 per 1 cm2 of the plaque (37.4 [15.3; 76]). Marker expression was heterogeneous: it was observed in all or only some endothelial cells of the newly formed vessel, and the expression intensity varied from weak to strong. Both CD34+LYVE-1+ and CD34+LYVE-1– vessel phenotypes were identified. A relationship between endothelial LYVE-1 expression and the structure or type of plaque was not established, except for the macrophage response. The density of LYVE-1+ vessels in atherosclerotic plaques correlated weakly with the overall macrophage response (r = 0.37; p = 0.03), more significantly with the number of anti-inflammatory M2 macrophages (r = 0.47; p = 0.005), especially for vessels with moderate and strong marker expression (r = 0.56; p = 0.0006).

Conclusion. The combined expression of LYVE-1 and CD34 in the endothelium of plaque neovessels was demonstrated for the first time, and a possible association between endothelial LYVE-1 expression in newly formed vessels and the reparative processes in atherosclerotic plaques was shown.