New blood vessels in atherosclerotic lesions are postulated to be responsible for plaque instability by acting as conduits for inflammatory cells. This study assessed the association between macrophage content of plaque caps of carotid atherosclerotic lesions, plaque vascularity, and endothelial-cell activation within these blood vessels. Carotid endarterectomy specimens from patients who underwent endarterectomy for carotid occlusive disease (ten symptomatic, six asymptomatic) were examined. Sequential transverse sections were obtained and were stained conventionally and immunohistochemically with CD 34 (an endothelial-cell marker) and CD 68 (a macrophage marker), as well as VCAM-1 and ICAM-1 (markers of endothelial-cell activation). Microvessel and macrophage counts were performed for the whole plaque and the plaque cap respectively. The differences in microvessel density, macrophage content, and ICAM-1 and VCAM-1 expression, between symptomatic and asymptomatic patients and in different plaque types were examined, as was the association between microvessel density and microvessel content of atherosclerotic lesions. Higher microvessel counts were observed in patients with symptomatic carotid occlusive disease (p < 0.01). Higher ICAM-1 and VCAM-1 expression was noted in new blood vessels in plaques obtained from patients with symptomatic carotid occlusive disease, compared with asymptomatic patients (p < 0.001 and p < 0.01 respectively). A close association was observed between macrophage content of the plaque cap and microvessel counts in atherosclerotic lesions (p < 0.0001), as well as ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) expression, in these microvessels. This study highlights the significance of neovascularity and endothelial-cell activation in the evolution of symptomatic carotid occlusive disease. Furthermore, it points to a relationship between the inflammatory process and angiogenesis within the plaque, which may be mediated through endothelial-cell activation.
Read full abstract