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dc.contributor.authorRiches-Suman, Kirsten*
dc.contributor.authorAlshanwani, A.R.*
dc.contributor.authorWarburton, P.*
dc.contributor.authorO'Regan, D.J.*
dc.contributor.authorBall, S.G.*
dc.contributor.authorWood, I.C.*
dc.contributor.authorTurner, N.A.*
dc.contributor.authorPorter, K.E.*
dc.date.accessioned2016-10-26T14:44:42Z
dc.date.available2016-10-26T14:44:42Z
dc.date.issued2014-09
dc.identifier.citationRiches-Suman K, Alshanwani A, Warburton P et al (2014) Elevated expression levels of microRNA-143/5 in saphenous vein smooth muscle cells from patients with type 2 diabetes drive persistent changes in phenotype and function. Journal of Molecular and Cellular Cardiology. 74: 240-250.
dc.identifier.urihttp://hdl.handle.net/10454/10084
dc.descriptionYes
dc.description.abstractType 2 diabetes (T2DM) promotes premature atherosclerosis and inferior prognosis after arterial reconstruction. Vascular smooth muscle cells (SMC) respond to patho/physiological stimuli, switching between quiescent contractile and activated synthetic phenotypes under the control of microRNAs (miRs) that regulate multiple genes critical to SMC plasticity. The importance of miRs to SMC function specifically in T2DM is unknown. This study was performed to evaluate phenotype and function in SMC cultured from non-diabetic and T2DM patients, to explore any aberrancies and investigate underlying mechanisms. Saphenous vein SMC cultured from T2DM patients (T2DM-SMC) exhibited increased spread cell area, disorganised cytoskeleton and impaired proliferation relative to cells from non-diabetic patients (ND-SMC), accompanied by a persistent, selective up-regulation of miR-143 and miR-145. Transfection of premiR-143/145 into ND-SMC induced morphological and functional characteristics similar to native T2DM-SMC; modulating miR-143/145 targets Kruppel-like factor 4, alpha smooth muscle actin and myosin VI. Conversely, transfection of antimiR-143/145 into T2DM-SMC conferred characteristics of the ND phenotype. Exposure of ND-SMC to transforming growth factor beta (TGFβ) induced a diabetes-like phenotype; elevated miR-143/145, increased cell area and reduced proliferation. Furthermore, these effects were dependent on miR-143/145. In conclusion, aberrant expression of miR-143/145 induces a distinct saphenous vein SMC phenotype that may contribute to vascular complications in patients with T2DM, and is potentially amenable to therapeutic manipulation.
dc.language.isoen
dc.rights© 2014 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
dc.subjectType 2 diabetes
dc.subjectSmooth muscle cell
dc.subjectSaphenous vein
dc.subjectMicroRNA-143/145
dc.subjectTGFβ
dc.subjectDifferentiation
dc.titleElevated expression levels of microRNA-143/5 in saphenous vein smooth muscle cells from patients with type 2 diabetes drive persistent changes in phenotype and function
dc.status.refereedYes
dc.typeArticle
dc.type.versionAccepted manuscript
dc.identifier.doihttps://doi.org/10.1016/j.yjmcc.2014.05.018
dc.rights.licenseCC-BY-NC-ND
refterms.dateFOA2018-07-25T14:36:45Z
dc.openaccess.statusopenAccess


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