Immune cells and vasa vasorum in the tunica media of atherosclerotic coronary arteries

Abstract

In coronary artery disease (CAD), the disruption of the tunica media immune privilege manifests as increased leukocyte infiltration and the formation of vasa vasorum. We aimed to characterize the immune privilege status of the tunica media in human coronary arteries (CAs) with atherosclerotic plaques, by comparing the abundance and composition of immune-cell infiltrates within the individual arterial-wall layers, and by evaluating vasa vasorum neovascularization of the tunica media. The tissue samples were obtained from 36 symptomatic patients with diffuse CAD (aged 60-72 years) who underwent coronary endarterectomy. T and B cells, macrophages and endothelial cells in the CAs were detected by immunohistochemistry. Morphological analysis of CAs showed significant atherosclerotic changes in all specimens. In the media, we observed damage and loss of smooth muscle cells, destruction of the extracellular matrix architecture, and fibrosis. There were 43.3% of immune cells in the intima, 50% in the adventitia, and 6.7% in the media. In the media, 51.1% of the immune cells were T cells (p ˂ 0.001 compared to B cells and macrophages; ANOVA, Scheffe post hoc analysis), 23.5% were B cells, and 25.4% were macrophages. The number of vasa vasorum in the media was 1 in 38.9% of CAs, 2-3 in 36.1%, and ≥4 in 25% of CAs. Our results indicate that, in atherosclerotic CAs, the immune privilege of the media is disrupted by the infiltration of T and B cells, macrophages, and the presence of vasa vasorum.

FIGURE 1

(A) Fibroproliferation in the tunica intima of human atherosclerotic coronary arteries (the thickened tunica intima is between the two arrows, HE, 2.5×, bar = 500 µm); (B) Perivascular infiltration (arrows) around vasa vasorum in the tunica media (HE, 40×, bar = 50 µm); (C) B cells (arrows) and vasa vasorum in the tunica media (anti CD79, 40×, bar = 50 µm); (D) T cells (arrows) and vasa vasorum in the tunica media (anti CD3, 40×, bar = 50 µm); (E) Macrophages (arrows) and vasa vasorum in the tunica media (anti CD68, 40×); (F) Endothelial cells (arrows) of vasa vasorum in the tunica media (anti human von Willebrand factor, 63×, bar = 30 µm).

FIGURE 2

(A) Average number ± SD of B cells, T cells and macrophages in the tunica intima, tunica media and tunica adventitia of human atherosclerotic coronary arteries (CAs). *Significantly different number of immune cells (ANOVA, Scheffe post hoc test, p < 0.05 for all); (B) The percentage of CAs with different degrees of vascular density in the media; note that all CAs had one or more vasa vasorum in the tunica media.

FIGURE 3

Endothelial cells of vasa vasorum in the tunica media of human atherosclerotic coronary arteries [CAs] (anti-human von Willebrand factor, 40×, bar = 50 µm). The estimation of vasa vasorum density: degree 1 - one vessel in the section (A, arrow); degree 2 - two or three vessels in the section (B, arrows); and degree 3 - four or more vessels in section (C, arrows). Note that all CAs have one or more vasa vasorum in the tunica media.