Pulmonary Production of Soluble ST2 in Heart Failure.
BACKGROUND: Serum concentrations of ST2 (interleukin-1 receptor-like 1) represent a meaningful prognostic marker in cardiac diseases. Production of soluble ST2 (sST2) may be partially extracardiac. Identification of sST2 sources is relevant to design strategies for modulating its signaling. METHODS AND RESULTS: An experimental model of ischemic heart failure was used. sST2, membrane-bound ST2 (ST2L), and IL-33 were measured in lungs, heart, kidney, and liver by quantifying mRNA and protein expression in tissue samples obtained at different times (1, 2, 4, and 24 weeks). Primary human type II pneumocyte cell cultures were subjected to strain. sST2 was measured in samples of bronchial aspirate and serum obtained from patients treated with invasive respiratory support. In the experimental model, sST2 increased significantly from the first week in both lungs and myocardium, whereas ST2L/IL-33 response was unfavorable in lungs (decrease) and favorable in myocardium (increase). No changes were observed in liver and kidneys. ST2 immunostaining was intensely observed in alveolar epithelium, and sST2 was secreted by primary human type II pneumocytes in response to strain. sST2 levels in lung aspirates were substantially higher in the presence of cardiogenic pulmonary edema (median, 228 [interquartile range, 28.4-324.0] ng/mL; P<0.001) than bronchopneumonia (median, 5.5 [interquartile range, 1.6-6.5]) or neurological disorders (median, 2.9 [interquartile range, 1.7-10.1]), whereas sST2 concentrations in serum did not differ. CONCLUSIONS: The lungs are a relevant source of sST2 in heart failure. These results may have implications for the progression of disease and the development of therapies targeting the ST2 system in patients with heart failure.
Pascual-Figal, DA; Pérez-Martínez, MT; Asensio-Lopez, MC; Sanchez-Más, J; García-García, ME; Martinez, CM; Lencina, M; Jara, R; Januzzi, JL; Lax, A
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