title: Inflammation and vascular smooth muscle cell dedifferentiation following carotid artery ligation.
abstract: Following vascular injury medial smooth muscle cells dedifferentiate and migrate through the internal elastic lamina where they form a neointima. The goal of the current study was to identify changes in gene expression that occur before the development of neointima and are associated with the early response to injury. Vascular injury was induced in C57BL/6 mice and inMyh11-creER(T2) mTmG reporter mice by complete ligation of the left carotid artery. Reporter mice were used to visualize cellular changes in the injured vessels. Total RNA was isolated from control carotid arteries or from carotid arteries 3 days following ligation of C57BL/6 mice and analyzed by Affymetrix microarray and quantitative RT-PCR. This analysis revealed decreased expression of mRNAs encoding smooth muscle-specific contractile proteins that was accompanied by a marked increase in a host of mRNAs encoding inflammatory cytokines following injury. There was also marked decrease in molecules associated with BMP, Wnt, and Hedgehog signaling and an increase in those associated with B cell, T cell, and macrophage signaling. Expression of a number of noncoding RNAs were also altered following injury with microRNAs 143/145 being dramatically downregulated and microRNAs 1949 and 142 upregulated. Several long noncoding RNAs showed altered expression that mirrored the expression of their nearest coding genes. These data demonstrate that following carotid artery ligation an inflammatory cascade is initiated that is associated with the downregulation of coding and noncoding RNAs that are normally required to maintain smooth muscle cells in a differentiated state.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and pherring@iupui.edu.
authors.forename: B Paul
authors.initials: BP
authors.lastname: Herring
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: April M
authors.initials: AM
authors.lastname: Hoggatt
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Griffith
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D054337:Cell Dedifferentiation; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009119:Muscle Contraction / Q000235:genetics; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D035683:MicroRNAs; D009124:Muscle Proteins; D012333:RNA, Messenger; D022661:RNA, Untranslated
keywords: inflammation; long noncoding RNA; microRNA; neointima; smooth muscle differentiation; vascular smooth muscle