Abstract Introduction Cardiopulmonary bypass (CPB) is an artificial device used to temporarily maintain cardiac and pulmonary activity and organ perfusion during cardiac surgery. Despite improvements, it is associated with significant adverse effects. CPB frequently induces systemic inflammatory response syndrome (SIRS), which manifests in particular as dysregulated cytokine secretion. This inflammatory reaction is responsible for significant morbidity, including organ dysfunction such as kidney and lung failure, prolonged stays in intensive care, and increased mortality. Understanding the inflammatory mechanisms associated with CPB is therefore crucial to improving patient care. Identifying new biomarkers that can predict the intensity of the inflammatory response, or new therapeutic targets capable of modulating it, is a major clinical challenge. Vasorin (Vasn) is a transmembrane protein mainly expressed in large vessels. It can be cleaved and found in soluble form in the circulation (sVasn). Vasn has recently been correlated with several inflammatory mediators and lung damage in animals. It could therefore constitute a new relevant biomarker of CPB-induced SIRS in humans. An increase in plasma Vasn concentration was observed in a pilot clinical study we conducted in collaboration with Amiens University Hospital. The aim of our work is therefore to evaluate whether circulating Vasn (sVasn) is capable of contributing to the development and/or modulation of inflammation, using an in vitro approach. Materials and Methods Human endothelial cells (HUVEC), human neutrophils (PNN) and THP-1 monocytes (Mo) were incubated with or without soluble recombinant Vasn (sVasn) at different time. RNA expression of pro and anti-inflammatory cytokines was assessed by RT-qPCR. Results sVasn significantly increases the expression of IL1β and IL6 and significantly decreases the expression of TNFα in HUVECs and PNNs. In THP-1 cells, sVasn appears to modulate the expression of inflammatory cytokines. Discussion Our results suggest that sVasn plays a modulatory role in the inflammatory response. It promotes the expression of pro-inflammatory cytokines, particularly IL1β and IL6, in endothelial cells and neutrophils, while reducing the expression of TNFα. This differentiated regulation could reflect a specific involvement of Vasn in the post-CPB inflammatory response. Conclusion Soluble Vasn could have a deleterious effect in the context of post-CPB cardiac surgery. Indeed, it appears to be involved in increasing inflammation through elevated expression of certain cytokines. Its role as a biomarker or therapeutic target will need to be confirmed by further in vitro and in vivo studies.
Catel-Dobel et al. (Fri,) studied this question.