Altered cellular responses to serum mitogens, including platelet‐derived growth factor, in cultured smooth muscle cells derived from arteries of patients with moyamoya disease

Abstract

Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. The etiology is unknown. We examined cultured arterial smooth muscle cells (SMC) from scalp arteries of five patients with moyamoya disease. In this study we investigated the responsiveness of the cells in culture to serum mitogens including platelet-derived growth factor (PDGF), a major mitogen of SMC, and compared the response to that of cells derived from age-matched control patients. SMC from patients with moyamoya disease proliferated less rapidly in a medium with 15% serum than did control SMC and responded poorly to the addition of PDGF to 5% serum. PDGF alone did not stimulate SMC in a quiescent state to initiate DNA synthesis in moyamoya disease, without serum factors other than bovine serum albumin, though it significantly stimulated the controls. Simultaneous additions of epidermal growth factor, insulin-like growth factor-I, and PDGF stimulated initiation of DNA synthesis in cells from moyamoya disease, but not as much as PDGF alone did in the controls. Although direct correlations with the pathogenesis of the disease remain to be clarified, the results indicate altered interrelations between serum factors and the cellular responses in vessels of moyamoya disease.

Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease.

“…25 vivo. Therefore, further study is necessary to elucidate the role of these growth factors in the pathogenesis of moyamoya disease.…”

The Diverse Effects of a Chinese Medicine, Qing Nao Yi Zhi Fang, on the Proliferation of Human Arterial Smooth Muscle Cells and Endothelial Cells

“…When SMCs were cultured in MEM containing 10% FBS, the proliferation of HCSMC was significantly higher than that of HMSMC, as described previously. 10) For both HCSMC and HMSMC, the addition of 10% NRS produced a lower response compared with cells grown in MEM containing 10% FBS. In contrast, the cells cultured in MEM containing 10% QNYZS did not grow at all, even after 11 d (Fig.…”

“…[6][7][8] The etiology of the disease remains unknown, but we have postulated that alterations in cellular responses to growth factors and cytokines in vascular cells are responsible for the development of intimal thickening in moyamoya disease. 10) We recently found that differences in the responses to platelet-derived growth factor and interleukin-1 in moyamoya SMCs are involved in the mechanism of intimal thickening in moyamoya disease. 9) In the present study, QNYZ and QNYZS showed inhibitory activities on the proliferation of moyamoya SMCs as well as control SMCs.…”

“…For the present study, we used cells within 50% of the final population doubling levels that showed no signs of senescence in vitro 12,13) These cells were carefully examined for mycoplasma contamination by the method described previously. 10) For cell growth measurements, SMCs (1ϫ10 4 ) were cultured in 16 mm plastic dishes in 0.5 ml of MEM containing 10% FBS, 10% NRS, or 10% QNYZ serum at 37°C in a CO 2 incubator. To examine the effects of QNYZ, SMCs were cultured in 0.5 ml of MEM containing 10% FBS for 24 h, and the medium was replaced with MEM containing 10% FBS with or without QNYZ (100-1000 mg/ml).…”

Emodin inhibits tumor necrosis factor-α-induced migration and inflammatory responses in rat aortic smooth muscle cells

“…Eight-week-old male Sprague-Dawley rats were obtained from the Experimental Animal Center of China Medical University. Primary RASMCs were prepared from the aortas of rats by the method previously described (18) and cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco, Grand Island, NY) supplemented with 10% fetal bovine serum (FBS, Hyclone, Logan, UT), 2 mmol/l glutamine, 100 U/ml penicillin, and 100 µg/ml streptomycin at 37˚C in a humidified 5% CO 2 atmosphere. The purity of the cultured RASMCs was verified by immunostaining with a monoclonal antibody against smooth muscle-specific α-actin.…”