Smooth Muscle Cell Proliferation and Localization of Macrophages and T Cells in the Occlusive Intracranial Major Arteries in Moyamoya Disease

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Abstract

Background and Purpose

Stenosis or occlusion due to fibrocellular intimal thickening in the intracranial major arteries is thought to be the primary lesion in moyamoya disease, but its etiology and pathogenesis are unknown. The present study was designed to analyze cellular components of the lesions and their pathological process.

Methods

Stenotic or occlusive intracranial arterial lesions were collected from six autopsied patients who died of moyamoya disease. The cellular components were analyzed by immunohistochemical staining using cell-type-specific monoclonal antibodies. The sections were also immunostained for proliferating cell nuclear antigen (PCNA) to detect proliferating cells and for two different types of intermediate filaments, desmin and vimentin, to evaluate phenotypes of the intimal smooth muscle cells.

Results

The thickened intima was composed predominantly of smooth muscle cells with an admixture of some macrophages and T cells. Macrophages and T cells were scattered in the superficial layer of the intimal thickening, and these were occasionally associated with organization of fibrin thrombi. Proliferating smooth muscle cells, indicated by PCNA-positive nuclei and muscle actin-positive cytoplasm, were found in the thickened intima in four patients. Immunohistochemical staining for intermediate filaments revealed intimal smooth muscle cells showing positive staining for vimentin and negative staining for desmin, compatible with the phenotype of synthetic smooth muscle cells.

Conclusions

The present study provides evidence that smooth muscle cells are proliferating in the occlusive lesions in intracranial major arteries in moyamoya disease. The colocalization of inflammatory cells and PCNA-positive cells suggests that inflammatory stimuli may induce proliferative response of smooth muscle cells and contribute to the formation of the intracranial occlusive lesions in moyamoya disease.

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