RESUMO
The interleukin-1 family is associated with innate immunity and inflammation. The latter has been linked to the genesis of cardiovascular diseases. We, therefore, investigated whether interleukin-1 beta (IL-1ß) is activated during arterialization of vein grafts. First, we examined the activation of IL-1ß using the rat arterialized jugular vein serially sampled for up to 90 days. IL-1ß expression increased 18 times on day 1 in the arterialized rat jugular vein and remained five times above nonarterialized vein levels for up to 90 days. Similarly, IL-1ß expression increased early (1-5 days) in human vein graft autopsy samples compared with late phases (1-4 years). Activation was also detected in ex vivo arterialized human saphenous veins. Upon stratification of the results, we uncovered a T allele promoter attenuating effect in IL-1ß activation in response to hemodynamic stress. Altogether, the results show that IL-1ß is activated during arterialization of vein grafts in rats and humans, and this response is modulated by -511C/T IL-1ß gene polymorphism. It is tempting to speculate that the activation of IL-1ß, and consequently local inflammation, modulates early vascular remodeling and that the gene polymorphism may be useful in predicting outcomes or assisting in interventions.
RESUMO
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 ß1-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.