BACKGROUND: An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic, and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulate cardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients. METHODS AND RESULTS: We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line to express the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction, and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-type natriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patients with diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levels than patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels. CONCLUSIONS: This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.
BACKGROUND: An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic, and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulate cardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients. METHODS AND RESULTS: We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line to express the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction, and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-type natriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patients with diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levels than patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels. CONCLUSIONS: This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.
Authors: Hannah Fish-Trotter; Jane F Ferguson; Nirav Patel; Pankaj Arora; Norrina B Allen; Katherine N Bachmann; Lori B Daniels; Muredach P Reilly; Joao A C Lima; Thomas J Wang; Deepak K Gupta Journal: Circ Heart Fail Date: 2020-06-08 Impact factor: 8.790
Authors: Antonio Abbate; Stefano Toldo; Carlo Marchetti; Jordana Kron; Benjamin W Van Tassell; Charles A Dinarello Journal: Circ Res Date: 2020-04-23 Impact factor: 17.367
Authors: Dorota Formanowicz; Maria Wanic-Kossowska; Elżbieta Pawliczak; Marcin Radom; Piotr Formanowicz Journal: Sci Rep Date: 2015-12-16 Impact factor: 4.379