Information about the in vivo location, shape, degradation, or erosion rate of injected in situ gelating hydrogels can be obtained with magnetic resonance imaging (MRI). Herein, an injectable supramolecular ureidopyrimidinone-based hydrogel (UPy-PEG) is functionalized with a modified Gadolinium(III)-DOTA complex (UPy-Gd) for contrast enhanced MRI. The contrast agent is designed to supramolecularly interact with the hydrogel network to enable high-quality imaging of this hydrogel. The applicability of the approach is demonstrated with successful visualization of the Gd-labeled UPy-PEG hydrogel after targeted intramyocardial catheter injection in a pig heart.

BackgroundThe interleukin‐33 (IL‐33)/suppressor of tumorigenicity 2 (ST2) pathway is suggested to play an important role in fibrosis, remodelling and the progression of heart failure (HF). Increased soluble (sST2) levels are associated with adverse outcome in the average HF population. Less is known about sST2 levels in end‐stage HF. Therefore, we studied sST2 levels in end‐stage HF and the effect of unloading by left ventricular assist device (LVAD) support on sST2 levels.Method and resultsSerial plasma measurements of sST2 were performed pre‐implantation and 1, 3 and 6 months after (LVAD) implantation in 38 patients. sST2 levels were elevated in end‐stage HF just prior to LVAD implantation (74.2 ng/mL [IQR 54.7‐116.9]; normal <35 ng/mL) and decreased substantially during LVAD support, to 29.5 ng/mL [IQR 24.7‐46.6](P < .001). Patients with INTERMACS profile I had significantly higher sST2 levels compared to patients in profile II and profile III. A moderate correlation was found between sST2 and C‐reactive protein (r = .580, P < .010).ConclusionLevels of sST2 are elevated in end‐stage HF patients with variability that suggests multiple inputs to a pro‐inflammatory and pro‐fibrotic pathway. Cardiogenic shock and increased C‐reactive protein levels are associated with higher sST2 levels. LVAD support results in a significant drop in sST2 levels with normalization within 3 months postimplantation. This suggests that LVAD support leads to lessening of fibrosis and inflammation, which might eventually be used to target medical policy: explantation of the LVAD versus permanent use or cardiac transplantation.

The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway is a potential pathophysiological mediator of cardiac fibrosis. Soluble ST2 (sST2) is one of the main isoforms of ST2 with strong prognostic value in cardiac disease. The exact role of sST2 in cardiac fibrosis is unknown. The aim of this study was (1) to investigate myocardial expression of the IL-33/ST2 pathway in relation to myocardial fibrosis in end-stage heart failure patients and (2) to study whether plasma sST2 is associated with histologically determined cardiac fibrosis. In 38 patients undergoing left ventricular assist device implantation, mRNA expression of sST2, total ST2, and IL-33 was measured in cardiac tissue obtained during the implantation. In the same tissue, histological fibrosis was digitally quantified and mRNA expression of pro-fibrotic signaling molecules, connective tissue growth factor (CTGF) and transforming growth factor beta 1 (TGFβ1), was measured. In addition, plasma levels of sST2 were determined. Expression levels of IL-33/ST2 pathway factors in myocardial tissue were significantly associated with cardiac fibrosis and the expression levels of CTGF and TGFβ1. Plasma levels of sST2 did not correlate with tissue expression of ST2, the amount of fibrosis or myocardial expression of pro-fibrotic signaling proteins. The interleukin-33/ST2 pathway is expressed in the failing human heart and its expression is associated with cardiac fibrosis and pro-fibrotic signaling proteins, suggesting a role in pro-fibrotic myocardial remodeling. Soluble ST2 levels in the circulation did not correlate with the amount of cardiac fibrosis or myocardial ST2 expression, however. Therefore, other pathophysiological processes such as inflammation might also substantially affect sST2 plasma levels.Electronic supplementary materialThe online version of this article (10.1007/s12265-017-9775-8) contains supplementary material, which is available to authorized users.