"Leukemia inhibitory factor" as novel mediator of vascular calcification

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Medial vascular calcification (VC) occurs during aging, diabetes and chronic renal failure. The calcification of the vasculature has been recognized as an important risk factor for cardiovascular mortality. Vascular calcification is an active process mediated by vascular smooth muscle cells. This process is regulated by a complex network of signaling cascades. Until now, no therapeutic treatment is available. This project aims to investigate a newly identified mediator of VC, which could be of major therapeutic relevance.Aim of this study is to investigate the role of the Leukemia inhibitory factor (LIF) and its signaling network during vascular calcification. Proteomic experiments in plasma of VC animal model identified a dramatic downregulation of the soluble LIF-receptor, which presumably acts as endogenous LIF-antagonist. Preliminary experiments indicate, that LIF is increasingly expressed during VC and strongly augments VC. Silencing of LIF can blunt osteogenic remodeling of vascular smooth muscle cells. This study will investigate the precise function of LIF during VC. Furthermore, the signaling networks mediating the effects of LIF in the vasculature will be identified. Further experiments will investigate whether blockade of LIF or its signaling pathways may reduce VC as therapeutic target.These studies can identify a novel critical regulator of vascular calcification and its intracellular pathways. LIF and its soluble receptor as antagonist could be pharmacologically easily accessible targets. These observations can therefore be of direct translational importance for the clinical treatment of VC.