Angiogenesis in carotid atherosclerosis: the association with morphological features of plaque instability

Abstract

Abstract Background Intimal angiogenesis is a recognized feature of the atherosclerotic process. It has been described in the context of unstable coronary atherosclerotic lesions. The aims of this study were to assess the association between angiogenesis in atherosclerotic plaques and microscopic features of plaque instability, in particular intraplaque haemorrhage. Methods Consecutive patients undergoing carotid endarterectomy for carotid stenosis were included in the study. Endarterectomy specimens were examined and divided into their constituent atherosclerotic lesions. Histological sections were prepared and stained with haematoxylin and eosin, and immunohistochemically with an endothelial cell marker (CD34). Each lesion was classified according to the American Heart Association classification of atherosclerotic lesions. The size of plaque haemorrhage was measured in transverse histological sections using computerized image analysis. Haemorrhagic lesions were classified according to the size of haemorrhagic area (under 50 per cent of section area; over 50 per cent of section area). Microvessel counts were performed in CD34-stained sections at × 400 magnification and were verified with computerized image analysis. The Kruskal–Wallis test was used to study the differences in microvessel count in different atherosclerotic plaque types. Results A total of 239 atherosclerotic lesions from 73 patients was available for analysis, of which 73 were early lesions, 74 were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque haemorrhage, of which 28 involved less than 50 per cent of the plaque section area. In 61 lesions the haemorrhage area was over 50 per cent of the section area. There were higher microvessel counts in plaques containing more than 50 per cent haemorrhage (median 277 (range 43–467)) compared with those containing less than 50 per cent (172 (57–372)) and non-haemorrhagic plaques (81 (7–389)) (P < 0·0001). Higher microvessel counts were observed in unstable atherosclerotic lesions (median 252 (range 43–467)), compared with stable fibroatheromas (106 (14–302)) and early atherosclerotic lesions (55 (7–237)) (P < 0·0001). Conclusion There are strong associations between plaque vascularity and presence and size of haemorrhage within atherosclerotic lesions, as well as features of plaque instability. This finding highlights the likely significance of these new blood vessels in the development of plaque instability and subsequent risk of stroke.