title: MicroRNA regulation of endothelial homeostasis and commitment-implications for vascular regeneration strategies using stem cell therapies.
abstract: Human embryonic (hESC) and induced pluripotent (hiPSC) stem cells have broad therapeutic potential in the treatment of a range of diseases, including those of the vascular system. Both hESCs and hiPSCs have the capacity for indefinite self-renewal, in addition to their ability to differentiate into any adult cell type. These cells could provide a potentially unlimited source of cells for transplantation and, therefore, provide novel treatments, e.g. in the production of endothelial cells for vascular regeneration. MicroRNAs are short, noncoding RNAs that act posttranscriptionally to control gene expression and thereby exert influence over a wide range of cellular processes, including maintenance of pluripotency and differentiation. Expression patterns of these small RNAs are tissue specific, and changes in microRNA levels have often been associated with disease states in humans, including vascular pathologies. Here, we review the roles of microRNAs in endothelial cell function and vascular disease, as well as their role in the differentiation of pluripotent stem cells to the vascular endothelial lineage. Furthermore, we discuss the therapeutic potential of stem cells and how knowledge and manipulation of microRNAs in stem cells may enhance their capacity for vascular regeneration.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scott
authors.forename: Komal
authors.initials: K
authors.lastname: Loya
authors.forename: Joanne
authors.initials: J
authors.lastname: Mountford
authors.forename: Graeme
authors.initials: G
authors.lastname: Milligan
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010084:Oxidation-Reduction; D012038:Regeneration; D015398:Signal Transduction; D014652:Vascular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D035683:MicroRNAs
keywords: CVD; EC; EPC; Embryonic stem cells; Free radicals; Induced pluripotent stem cells; MicroRNA; Pluripotency; ROS; Regenerative medicine; VEGF; Vascular endothelial cells; cardiovascular disease; endothelial cell; endothelial progenitor cell; hESC; human embryonic stem cell; iPSC; induced pluripotent stem cell; mESC; miRNA; microRNA; murine embryonic stem cell; reactive oxygen species; vascular endothelial growth factor