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Hypoxic remodelling of Ca2+ signalling in proliferating human arterial smooth muscle

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Abstract

Ca2+ homeostasis in proliferating smooth muscle (SM) cells strongly influences neointima formation, which can cause failure of coronary artery bypass surgery. During surgical procedures and subsequent revascularization, SM cells are also exposed to a period of hypoxia. Problems with bypass surgery in general involve neointima formation which is in turn dependent on SM proliferation and migration. Here, we have directly monitored [Ca2+]i fluorimetrically in proliferating internal mammary artery (IMA) SM cells, and investigated how this is modulated by chronic hypoxia (CH; 24 h, 2.5% O2). IMA is the most successful replacement conduit vessel in bypass grafts. Basal [Ca2+]i was unaffected by CH, but removal of extracellular Ca2+ evoked far smaller reductions in [Ca2+]i than were seen in normoxic cells. Voltage-gated Ca2+ entry was suppressed in CH cells, and this was attributable to activation of the transcriptional regulator, hypoxia inducible factor. Furthermore, the relative contributions to voltage-gated Ca2+ entry of L- and T-type Ca2+ channels was markedly altered, with T-type channels becoming functionally more important in CH cells. Agonist-evoked mobilization of Ca2+ from intracellular stores was not affected by CH, whilst subsequent capacitative Ca2+ entry was modestly suppressed. Our data provide novel observations of the remodelling of Ca2+ homeostasis by CH in IMASM cells which may contribute to their superior patency as coronary bypass grafts.

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Acknowledgements

This work was supported by The British Heart Foundation.

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Author notes

  1. Parvinder K. Aley

    Present address: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK

Authors and Affiliations

  1. Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health & Therapeutics, University of Leeds, Level 10, Worsley Building, Leeds, LS2 9JT, UK

    Parvinder K. Aley, Jenny A. Wilkinson, Claudia C. Bauer, John P. Boyle, Karen E. Porter & Chris Peers

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  1. Parvinder K. Aley
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  2. Jenny A. Wilkinson
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Correspondence to Chris Peers.

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Aley, P.K., Wilkinson, J.A., Bauer, C.C. et al. Hypoxic remodelling of Ca2+ signalling in proliferating human arterial smooth muscle. Mol Cell Biochem 318, 101–108 (2008). https://doi.org/10.1007/s11010-008-9861-y

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  • DOI: https://doi.org/10.1007/s11010-008-9861-y

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