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-1β) is activated during arterialization of vein grafts. First, we examined the activation of IL-1β using the rat arterialized jugular vein serially sampled for up to 90 days. IL-1β 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-1β 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-1β activation in response to hemodynamic stress. Altogether, the results show that IL-1β is activated during arterialization of vein grafts in rats and humans, and this response is modulated by -511C/T IL-1β gene polymorphism. It is tempting to speculate that the activation of IL-1β, and consequently local inflammation, modulates early vascular remodeling and that the gene polymorphism may be useful in predicting outcomes or assisting in interventions.
Highlights
Autologous coronary artery bypass graft (CABG) surgery is a common procedure used for revascularization in ischemic heart disease
Using a combination of in vivo and ex vivo vascular methods, we provide evidence that IL-1β is modulated in arterialized vein segments of animal and human samples and that an IL-1β genetic polymorphism modulates this response, which may be useful for predicting outcomes or to assist interventions to modulate the early inflammatory response associated with vein graft arterialization in the future
This profile is consistent with the idea of its role in early vein graft intimal hyperplasia because IL-1β production is localized to the developing neointima
Summary
Autologous coronary artery bypass graft (CABG) surgery is a common procedure used for revascularization in ischemic heart disease. Several aspects of the atherogenesis process have been described and involve complex interaction of inflammatory cells and vascular cells [2,3,4,5]. Researchers showed that the reduction of the risk of cardiovascular events is proportional to the reduction of the inflammatory response [11] This evidence highlights the importance of inflammation in the development of cardiovascular complications. We carefully demonstrate the time course activation of IL-1β upregulation using an in vivo rat model We validated this observation in samples from arterialized human saphenous vein and autopsy samples and provide evidence for the influence of-511C/T IL-1β polymorphism in IL-1β expression in the response to increased hemodynamic stress
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