Activation of Interleukin-1 Beta in Arterialized Vein Grafts and the Influence of the -511C/T IL-1 beta Gene Polymorphism

Abstract

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-1 beta) is activated during arterialization of vein grafts. First, we examined the activation of IL-1 beta using the rat arterialized jugular vein serially sampled for up to 90 days. IL-1 beta 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-1 beta 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-1 beta activation in response to hemodynamic stress. Altogether, the results show that IL-1 beta is activated during arterialization of vein grafts in rats and humans, and this response is modulated by -511C/T IL-1 beta gene polymorphism. It is tempting to speculate that the activation of IL-1 beta, and consequently local inflammation, modulates early vascular remodeling and that the gene polymorphism may be useful in predicting outcomes or assisting in interventions.