Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10142918 | Cellular Signalling | 2018 | 50 Pages |
Abstract
Vascular smooth muscle cells (VSMCs) are the major cell type in blood vessels. Unlike many other mature cell types in the adult body, VSMC do not terminally differentiate but retain a remarkable plasticity. Fully differentiated medial VSMCs of mature vessels maintain quiescence and express a range of genes and proteins important for contraction/dilation, which allows them to control systemic and local pressure through the regulation of vascular tone. In response to vascular injury or alterations in local environmental cues, differentiated/contractile VSMCs are capable of switching to a dedifferentiated phenotype characterized by increased proliferation, migration and extracellular matrix synthesis in concert with decreased expression of contractile markers. Imbalanced VSMC plasticity results in maladaptive phenotype alterations that ultimately lead to progression of a variety of VSMC-driven vascular diseases. The nature, extent and consequences of dysregulated VSMC phenotype alterations are diverse, reflecting the numerous environmental cues (e.g. biochemical factors, extracellular matrix components, physical) that prompt VSMC phenotype switching. In spite of decades of efforts to understand cues and processes that normally control VSMC differentiation and their disruption in VSMC-driven disease states, the crucial molecular mechanisms and signalling pathways that shape the VSMC phenotype programme have still not yet been precisely elucidated. In this article we introduce the physiological functions of vascular smooth muscle/VSMCs, outline VSMC-driven cardiovascular diseases and the concept of VSMC phenotype switching, and review molecular mechanisms that play crucial roles in the regulation of VSMC phenotypic plasticity.
Keywords
GSK3βTGFβRhoAFGFMSCMIRTCFSRFKLFMKL1CADASILF-actinIRS-1MLCKPDGFVSMCG-actinPIP3MLCPmTORC1SBEPDK1SCAIECMROCCMLC20PI3KEGFPIP2TCEIGFSMCMRTFPAHTET2globular actinMAPKcerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathyApoeapolipoprotein EDESDrug-eluting stentsinsulin receptor substrate-1cardiovascular diseasecoronary artery diseasestransforming growth factor-βPhenotype switchingforkhead Box OCVDmicroRNAsmyosin light chain kinaseSmooth muscle cellVascular smooth muscle cellEndothelial cellMesenchymal stem cellCADepidermal growth factorTernary complex factorKrüppel-like factorsmooth muscle Vascular smooth muscleSmad binding elementplatelet derived growth factorfibroblast growth factorInsulin-like growth factorserum response factorFoxOMyosin light chain phosphatasephosphatidylinositol-3-kinasePulmonary arterial hypertensionMegakaryoblastic leukemiaExtracellular matrixBMPSignalling pathwaysMyocardinNitric oxideMammalian target of rapamycin complex 1Phosphoinositide-dependent kinase-1Bone morphogenetic proteinmitogen-activated protein kinaseRho-associated protein kinaseAdherens junctionGlycogen synthase kinase-3βRock
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Authors
Agne Frismantiene, Maria Philippova, Paul Erne, Therese J. Resink,