Substrate-induced phenotypic switches of human smooth muscle cells: anin vitrostudy of in-stent restenosis activation pathways

Journal of the Royal Society Interface - Tập 8 Số 58 - Trang 641-649 - 2011
Anna Guildford1, Helen Stewart2, Christopher G. Morris1, Matteo Santin1
1School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton BN2 4GJ, UK
2Brighton and Sussex Medical School, Falmer Campus, Brighton, UK

Tóm tắt

In-stent restenosis is a clinical complication following coronary angioplasty caused by the implantation of the metal device in the atherosclerotic vessel. Histological examination has shown a clear contribution of both inflammatory and smooth muscle cells (SMCs) to the deposition of an excess of neointimal tissue. However, the sequence of events leading to clinically relevant restenosis is unknown. This paper aims to study the phenotype of SMCs when adhering on substrates and exposed to biochemical stimuli typical of the early phases of stent implantation. In particular, human SMC phenotype was studied when adhering on extracellular matrix-like material (collagen-rich gel), thrombus-like material (fibrin gel) and stent material (stainless steel) in the presence or absence of a platelet-derived growth factor (PDGF) stimulus. Cells on the collagen and fibrin-rich substrates maintained their contractile phenotype. By contrast, cells on stainless steel acquired a secretory phenotype with a proliferation rate 50 per cent higher than cells on the natural substrates. Cells on stainless steel also showed an increase in PDGF-BB receptor expression, thus explaining the increase in proliferation observed when cells were subject to PDGF-BB stimuli. The stainless steel substrate also promoted a different pattern of β1-integrin localization and an altered expression of hyaluronan (HA) synthase isoforms where the synthesis of high-molecular-weight HA seemed to be favoured. These findings highlighted the induction of a phenotypic pattern in SMC by the stainless steel substrate whereby the formation of a HA-rich neointimal tissue is enhanced.

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Tài liệu tham khảo

10.1586/17434440.2.4.429

10.1161/01.CIR.99.1.44

10.1016/S0140-6736(04)17275-9

10.1161/01.ATV.0000131783.74034.97

10.1161/01.CIR.0000019071.72887.BD

10.1002/jbm.a.32100

10.1002/jbm.a.31204

10.1016/S0008-6363(98)00232-6

10.1074/jbc.M105490200

10.1074/jbc.M303945200

10.1016/S0006-291X(02)00592-2

Kosaki R., 1999, Overproduction of hyaluronan by expression of the hyaluronan synthase Has2 enhances anchorage-independent growth and tumorigenicity, Cancer Res., 59, 1141

10.1016/S0898-6568(00)00096-6

10.1161/01.HYP.0000062882.42265.88

Chiarugi P., 2002, New perspective in PDGF receptor downregulation: the main role of phosphotyrosine phosphatises, J. Cell Sci., 115, 2219, 10.1242/jcs.115.10.2219

Guildford A. L., Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents, Int. J. Cardiol.

10.1159/000265565

10.1016/S0008-6363(01)00399-6

10.1016/j.bbrc.2004.10.031

10.1161/01.HYP.35.1.255

10.1161/01.RES.76.2.209

10.1016/S0002-9440(10)63464-5

10.1164/rccm.200408-1046OC

10.1172/JCI119472

10.1016/S0955-0674(98)80144-0

10.1083/jcb.132.1.239

10.1161/hh0701.089749

10.1083/jcb.132.4.741

10.1016/j.biomaterials.2008.04.005

10.1042/0264-6021:3480029

10.1146/annurev.cellbio.23.090506.123337

10.2174/092986709788186138

10.1161/01.RES.0000199263.67107.c0

10.1006/abbi.2001.2507

10.1016/j.matbio.2008.01.007

10.1161/01.ATV.19.4.1004

10.1161/01.RES.0000119169.87429.A0

10.1002/jcp.20468

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Journal of the Royal Society Interface

Tập 8 Số 58

641-649

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