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MicroRNA‐21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells
Alshanwani, A.R. Riches-Suman, Kirsten O'Regan, D.J. Wood, I.C. Turner, N.A. Porter, K.E.
Alshanwani, A.R.
Riches-Suman, Kirsten
O'Regan, D.J.
Wood, I.C.
Turner, N.A.
Porter, K.E.
Publication Date
2018-07
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© 2018 International Union of Biochemistry and Molecular Biology. This is the peer reviewed version of the following article: Alshanwani AR, Riches-Suman K, O’Regan DJ et al (2018) MicroRNA-21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells. IUBMB Life. 70(7): 649-657, which has been published in final form at https://doi.org/10.1002/iub.1751. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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22/03/2018
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Abstract
Cardiovascular disease is a leading cause of morbidity and mortality. Smooth muscle cells (SMC) comprising the vascular wall can switch phenotypes from contractile to synthetic, which can promote the development of aberrant remodelling and intimal hyperplasia (IH). MicroRNA‐21 (miR‐21) is a short, non‐coding RNA that has been implicated in cardiovascular diseases including proliferative vascular disease and ischaemic heart disease. However, its involvement in the complex development of atherosclerosis has yet to be ascertained. Smooth muscle cells (SMC) were isolated from human saphenous veins (SV). miR‐21 was over‐expressed and the impact of this on morphology, proliferation, gene and protein expression related to synthetic SMC phenotypes monitored. Over‐expression of miR‐21 increased the spread cell area and proliferative capacity of SV‐SMC and expression of MMP‐1, whilst reducing RECK protein, indicating a switch to the synthetic phenotype. Furthermore, platelet‐derived growth factor BB (PDGF‐BB; a growth factor implicated in vasculoproliferative conditions) was able to induce miR‐21 expression via the PI3K and ERK signalling pathways. This study has revealed a mechanism whereby PDGF‐BB induces expression of miR‐21 in SV‐SMC, subsequently driving conversion to a synthetic SMC phenotype, propagating the development of IH. Thus, these signaling pathways may be attractive therapeutic targets to minimise progression of the disease.
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Alshanwani AR, Riches-Suman K, O’Regan DJ et al (2018) MicroRNA-21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells. IUBMB Life. 70(7): 649-657.
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