Abstract
The global expression profile of the arterialized rat jugular vein was established to identify candidate genes and cellular pathways underlying the remodeling process. The arterialized jugular vein was analyzed on days 3 and 28 post-surgery and compared with the normal jugular vein and carotid artery. A gene array platform detected 9846 genes in all samples. A heatmap analysis uncovered patterns of gene expression showing that the arterialized vein underwent a partial transition from vein to artery from day 3 to 28 post-surgery. The same pattern was verified for 1845 key differentially expressed genes by performing a pairwise comparison of the jugular vein with the other groups. Interestingly, hierarchical clustering of 60 genes with altered expression on day 3 and day 28 displayed an expression pattern similar to that of the carotid artery. Enrichment analysis results and the network relationship among genes modulated during vein arterialization showed that collagen might play a role in the early remodeling process. Indeed, the total collagen content was increased, with the augmented expression of collagen I, collagen IV, and collagen V in arterialized veins. Additionally, there was an increase in the expression of versican and Thy-1 and a decrease in the expression of biglycan and β1-integrin. Overall, we provide evidence that vein arterialization remodeling is accompanied by consistent patterns of gene expression and that collagen may be an essential element underlying extracellular matrix changes that support the increased vascular wall stress of the new hemodynamic environment.
Highlights
Coronary artery bypass graft surgery is a widely used procedure to revascularize the ischemic myocardium
We found that the pattern of gene expression of arterialized jugular veins is still close to vein expression profile more similar to the expression profile of the carotid artery
We found that the extracellular matrix is remodeled during the process of arterialization, and collagens may have a central role in orchestrating early molecular events
Summary
Coronary artery bypass graft surgery is a widely used procedure to revascularize the ischemic myocardium. The morphological changes that occur during vein graft arterialization have been well described; the molecular mechanism of the whole process has not been fully investigated. In terms of extracellular matrix, it has been described upregulation of TGF-β associated with increased expression of collagen I and collagen III [6]. The extracellular matrix is very dynamic and its remodeling is essential to adapt the vessel to the increased hemodynamic stress in vein graft procedure. We performed temporal high-throughput screening of the gene expression associated with the observed structural changes that occur during vein arterialization remodeling in the rat. We found that the extracellular matrix is remodeled during the process of arterialization, and collagens may have a central role in orchestrating early molecular events
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