In the present study, we used this canine model, the pathophysiology of vein graft implantation injury and identify novel therapeutic strategies. Specifically, we used Laser Capture Microdissection to isolate endothelial and medial layers for subsequent RNA extraction and transcription profiling. Our study focused on early transcriptional events that we believe to be key in dictating Folinic acid calcium salt pentahydrate outcome. We did not interrogate transcriptional changes of the neointima since this layer does not develop in this model, or in clinical vein grafts before 30 D. In fact IH is not significant in this model before 60�C90 days. Future work is focused on interrogating neointimal transcriptome in a longterm model of canine vein graft failure LCM yielded highly 
enriched EC and SMC samples allowing the study of cell specific transcriptional changes. To our knowledge, this is the first study using this approach. Unsupervised PCA analysis of our gene chips demonstrated that graft EC and SMC genes formed time dependent clusters with maximal transcriptional changes appearing 12 to 24 H following implantation, and diminishing over the 30 D time period. This tapered response suggests that early intervention during the peri-operative period may be sufficient to prevent/inhibit vein graft implantation injury, and therefore limit the development of IH. Supervised analysis of the transcriptional data depicted temporal modification of gene expression in EC and SMC. Interestingly, some genes were modified over continuous time-points, whereas others were either non-continuously modified or modified at a single time-point, highlighting the importance of defining optimal therapeutic windows for each given target. For example, the proinflammatory chemokine IL-8 was up-regulated in EC from 2 H up to 7 D, and in SMC from 12 H up to 7 D. This pattern of up-regulation in both cell types could be ideal for a targeted therapy aiming at interrupting early and mid pathogenic inflammatory culprits involved in vein graft implantation injury. In contrast, Col1A1 was up-regulated in both EC and SMC only at 30 D, suggesting that this extracellular matrix gene is likely a downstream participant in the pathogenesis of vein graft implantation injury, and key to the vascular remodeling that occurs in vein grafts. In addition this analysis also suggested that graft EC might be the first responders to vein graft implantation injury, as they obviate a change in their transcriptome as early as 2 H following implantation. In contrast, SMC do not show any significant changes at this early time-point. Gene ontology analysis on temporally, and differentially expressed genes indicated that implantation injury affected multiple ontological categories in both, EC and SMC. Enriched GO clusters included apoptosis, inflammatory and immune responses, mitosis and extracellular matrix reorganization. In EC, apoptosis related genes were up-regulated and peaked at 2 H following implantation confirming that rapid EC LOUREIRIN-B damage and loss was critical in triggering the cascade of events leading to vein graft injury. In contrast, apoptosis related genes were up-regulated and peaked in SMC at 12 H. The significance of increased expression of pro-apoptotic genes in medial SMC is still unclear. Several studies suggest that increased medial SMC apoptosis promotes vascular damage and influences the phenotypic switch of these cells from contractile to synthetic, therefore promoting IH.