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oai:docta.ucm.es:20.500.14352/1328772026-02-24T01:05:12Zcom_20.500.14352_14col_20.500.14352_15

CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation Martínez Martínez, Ernesto López Andrés, Natalia 616.12 cardiotrophin-1 fibroblasts galectin-3 heart failure inflammation Cardiología 2411 Fisiología Humana European Commission FP7 Programme European Research Area Network on Cardiovascular Diseases FP7-funded COST ADMIRE network ANR MRFOCUS Fight-HF Avenir investment program Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 µg/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1-treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF. Ministerio de Economía y Competitividad (España) Unión Europea Institut National de la Santé et de la Recherche Médicale (Francia) Centre de Recherche Industrielle et Technique (Algeria) Depto. de Fisiología Fac. de Medicina TRUE pub 2026-02-23T10:20:10Z 2026-02-23T10:20:10Z 2019-03-01 journal article VoR https://hdl.handle.net/20.500.14352/132877 0194-911X 10.1161/HYPERTENSIONAHA.118.11874 0194-911X eng CB16/11/00483 PI15/01909 PI15/02160 HOMAGE project 2012– 305507 FIBROTARGETS project 2013–602904 AC16/00020 BM1301 ANR-15- CE14-0032-02 ANR15-RHUS-0004 19. Martínez-Martínez E, Brugnolaro C, Ibarrola J, Ravassa S, Buonafine M, López B, Fernández-Celis A, Querejeta R, Santamaria E, Fernández-Irigoyen J, Rábago G, Moreno MU, Jaisser F, Díez J, González A, López-Andrés N. CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation. Hypertension. 2019 Mar;73(3):602-611 restricted access application/pdf American Heart Association