Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque

Objectives Characterize the phenotypic features of smooth muscle cells (SMCs) in the wall of human saccular intracranial aneurysms (sIAs). Methods and Results We investigated by means of immunohistochemistry the expression of the cytoskeletal differentiation markers α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin in 26 sIAs and 15 nonaneurysmal cerebral arteries. In addition, S100A4, a recently identified marker of dedifferentiated SMCs in atherosclerotic plaques, was also investigated. Six sIAs and 5 nonaneurysmal arteries were used for morphometric analysis. sIAs displayed a significant medial atrophy compared with nonaneurysmal cerebral arteries; moreover, sIA SMCs showed marked decrease of α-SMA and SMMHCs expression and disappearance of smoothelin. Unexpectedly, S100A4 was strongly up-regulated in media SMCs of sIAs. Conclusions In sIAs, media SMCs acquire a dedifferentiated phenotype and show de novo expression of S100A4, characteristic features of atherosclerotic plaque SMCs.