Macrophage subtypes in symptomatic carotid artery and femoral artery plaques

Abstract

Objective: To compare differences in macrophage heterogeneity and morphological composition between atherosclerotic plaques obtained from recently symptomatic patients with carotid artery disease and femoral plaques from patients with severe limb ischemia.

Design: Experimental study.

Methods: Plaques were obtained from 32 patients undergoing carotid endarterectomy and 25 patients undergoing common femoral endarterectomy or lower limb bypass. Macrophages and T cell numbers were detected in plaque sections by immunohistochemistry and anti CD68 and CD3 antibodies. Dual staining for CD68 and M1- and M2-macrophage markers and morphometric analysis of hematoxylin and eosin stained plaque sections was performed.

Results: Carotid plaques had significantly increased percentage areas of confluent lipid and leukocytic infiltrates. In contrast, areas of fibroconnective tissue were significantly greater in femoral plaques and percentage areas of confluent calcification and collagen were elevated. Carotid artery plaques had greater numbers per plaque area of macrophages and T cells consistent with a more inflammatory phenotype. Proportions displaying M1-activation markers were significantly increased in the carotid compared to femoral plaques whereas femoral plaques displayed a greater proportion of M2-macrophages.

Conclusion: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque.