Detalle Publicación

CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) axis in cardiac fibrosis and inflammation mechanistic insights and clinical implications
Autores: Martinez-Martinez, E.; Brugnolaro, C. ; Ibarrola, J.; Ravassa Albéniz, Susana; Buonafine, M. ; López Salazar, Begoña; Fernandez-Celis, A.; Querejeta, R.; Santamaria, E. ; Fernandez-Irigoyen, J.; Rabago Juan Aracil, Gregorio; Moreno Zulategui, María de Ujue; Jaisser, F.; Díez Martínez, Domingo Francisco Javier; González Miqueo, Aránzazu (Autor de correspondencia); Lopez-Andres, N. (Autor de correspondencia)
Título de la revista: HYPERTENSION
ISSN: 0194-911X
Volumen: 73
Número: 3
Páginas: 602 - 611
Fecha de publicación: 2019
Lugar: WOS
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 mu g/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.