Genome-Wide Microarray Analyses Identify the Protein C Receptor as a Novel Calcineurin/Nuclear Factor of Activated T Cells–Dependent Gene in Vascular Smooth Muscle Cell Phenotypic Modulation

• DOI: 10.1161/atvbaha.111.235960
• Publication Date: 2011-09-09T15:30:30Z
• Authors: Monica Y. Lee; Sean M. Garvey; Marcia L. Ripley; Brian R. Wamhoff
• Keywords: NFAT

Calcineurin (Cn) and the nuclear factor of activated T cells (NFAT) family transcription factors are critical in vascular smooth muscle cell (SMC) development pathology. Here, we used a genomics approach to identify validate NFAT gene targets during platelet-derived growth factor-BB (PDGF-BB)-induced SMC phenotypic modulation.Genome-wide expression arrays were genes both (1) differentially response PDGF-BB (2) whose differential was reduced by Cn inhibitor cyclosporin A A-285222. The 20 most pharmacologically sensitive validated quantitative reverse transcription-polymerase chain reaction analysis PDGF-BB-stimulated SMCs presence Cn/NFAT inhibitors, including VIVIT peptide. In all experiments, protein C receptor (PROCR) activation reduced. We showed that PROCR virtually absent untreated, quiescent SMCs. stimulation, however, induced significant promoter downstream Cn/NFAT-dependent manner. Mutation species-conserved, binding motif significantly attenuated PDGF-BB-induced activity, thereby distinguishing as first transcriptional activator date. Moreover, upregulated neointima early 7 days following acute injury rat carotid arteries.We hereby report novel, NFAT-dependent may be implicated restenosis consequent inward remodeling.