Detalle Publicación

ADAMTSL3 knock-out mice develop cardiac dysfunction and dilatation with increased TGF beta signalling after pressure overload

Autores: Rypdal, K. B. (Autor de correspondencia); Melleby, A. O.; Robinson, E. L.; Li, J.; Palmero, S.; Seifert, D. E.; Martin, D.; Clark, C.; López Salazar, Begoña; Andreassen, K.; Dahl, C. P.; Sjaastad, I.; Tonnessen, T.; Stokke, M. K.; Louch, W. E.; González Miqueo, Aránzazu; Heymans, S.; Christensen, G.; Apte, S. S.; Lunde, I. G.
Título de la revista: COMMUNICATIONS BIOLOGY
ISSN: 2399-3642
Volumen: 5
Número: 1
Páginas: 1392
Fecha de publicación: 2022
Resumen:
Heart failure is a major cause of morbidity and mortality worldwide, and can result from pressure overload, where cardiac remodelling is characterized by cardiomyocyte hypertrophy and death, fibrosis, and inflammation. In failing hearts, transforming growth factor (TGF)beta drives cardiac fibroblast (CFB) to myofibroblast differentiation causing excessive extracellular matrix production and cardiac remodelling. New strategies to target pathological TGF beta signalling in heart failure are needed. Here we show that the secreted glycoprotein ADAMTSL3 regulates TGF beta in the heart. We found that Adamtsl3 knock-out mice develop exacerbated cardiac dysfunction and dilatation with increased mortality, and hearts show increased TGF beta activity and CFB activation after pressure overload by aortic banding. Further, ADAMTSL3 overexpression in cultured CFBs inhibits TGF beta signalling, myofibroblast differentiation and collagen synthesis, suggesting a cardioprotective role for ADAMTSL3 by regulating TGF beta activity and CFB phenotype. These results warrant future investigation of the potential beneficial effects of ADAMTSL3 in heart failure.
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