Activated inflammatory cells are associated with plaque rupture in carotid artery stenosis

Background. Histologic studies of carotid plaques have demonstrated an association between symptomatic disease and plaque rupture. The purpose of this study was to characterize the cellular changes associated with plaque rupture. Methods. Carotid plaques were obtained from 61 patients undergoing carotid endarterectomy for established indications. Plaques were fixed in formalin, embedded in paraffin, and stained with hematoxylineosin and Movat pentachrome stain to demonstrate plaque structure. Each plaque was examined with light microscopy and classified as containing evidence of plaque rupture (n = 29) or no plaque rupture (n = 32). By using immunohistochemical staining, the fibrous cap was examined for the presence of smooth muscle cells (a-actin), macrophages (KP-I), T lymphocytes (UCHL-1), and cell activation (HLA-DR). Data were analyzed with chi-squared analysis. Results. With plaque rupture, macrophages and T lymphocytes were significantly more common than in specimens without evidence of rupture. Similarly, macrophages and T lymphocytes expressing HLA-DR were more often found in sections containing plaque rupture. Furthermore, vascular smooth muscle cells were more common with intact fibrous caps and were diminished with cap thinning. Conclusions. Rupture of the fibrous cap in carotid artery lesions is associated with increased numbers of macrophages and T lymphocytes, which are in an activated state. The activated inflammatory cells may release cytokines or metalloproteinases, which may be responsible for loss of the fibrous cap. Thus inflammation appears to play a role in the pathogenesis of the neurologic symptoms associated with carotid artery stenosis.