Martínez Martínez, ErnestoLópez Andrés, Natalia2026-02-232026-02-232019-03-0119. 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):602-6110194-911X10.1161/HYPERTENSIONAHA.118.11874https://hdl.handle.net/20.500.14352/132877European Commission FP7 Programme European Research Area Network on Cardiovascular Diseases FP7-funded COST ADMIRE network ANR MRFOCUS Fight-HF Avenir investment programMyocardial 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.engjournal article0194-911Xhttps://doi.org/10.1161/HYPERTENSIONAHA.118.1187430612490https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.118.11874restricted access616.12cardiotrophin-1fibroblastsgalectin-3heart failureinflammationCardiología2411 Fisiología Humana