Objective: 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 prior to the development of neointima and are associated with the early response to injury. Approach and Results: Vascular injury was induced in C57Bl/6 mice and in Myh11-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 down-regulated and microRNAs 1949 and 142 up-regulated. Several long noncoding RNAs showed altered expression that mirrored the expression of their nearest coding genes. Conclusions: These data demonstrate that following carotid artery ligation an inflammatory cascade is initiated that is associated with the down-regulation of coding and noncoding RNAs that are normally required to maintain smooth muscle cells in a differentiated state.
- vascular smooth muscle
- smooth muscle differentiation
- noncoding RNA
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