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(Circulation Research. 1999;85:912.)
© 1999 American Heart Association, Inc.

Cellular Biology

Increase in Prostaglandin E₂ Production by Interleukin-1ß in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease

Mari Yamamoto, Masaru Aoyagi, Naomi Fukai, Yoshiharu Matsushima, Kiyotaka Yamamoto

From the Department of Cell Biology (M.Y., M.A., N.F., K.Y.), Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo; and Department of Neurosurgery (M.A., Y.M.), Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Correspondence to Kiyotaka Yamamoto, PhD, Department of Cell Biology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173, Japan. E-mail kyama{at}tmig.or.jp

Abstract—Moyamoya disease is a progressive cerebrovascular occlusive disease that primarily affects children. The cause is unknown. We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and 8 control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated with interleukin-1ß (IL-1ß), prostaglandin E₂ (PGE₂) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, whereas the amounts of prostacyclin and thromboxane B₂ did not differ. IL-1ß–induced PGE₂ production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1ß significantly stimulated cell migration and DNA synthesis in control SMCs but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migration of moyamoya SMCs were caused by excessive secretion of PGE₂ and was reversed with indomethacin treatment. Immunofluorescence studies and Western blot analysis showed greater amounts of COX-2 protein expression in IL-1ß–stimulated moyamoya SMCs. These findings suggest that moyamoya SMCs respond to inflammatory stimuli to produce excess amounts of PGE₂ through the activation of COX-2, which increases vascular permeability and decreases vascular tone. This facilitates the exposure of vessels to blood constituents and promotes the development of intimal thickening in moyamoya disease.

Key Words: interleukin • moyamoya disease • muscle, smooth • prostaglandin

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