| First Author | Rypdal KB | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 1392 |
| PubMed ID | 36539599 | Mgi Jnum | J:332622 |
| Mgi Id | MGI:7411696 | Doi | 10.1038/s42003-022-04361-1 |
| Citation | Rypdal KB, et al. (2022) ADAMTSL3 knock-out mice develop cardiac dysfunction and dilatation with increased TGFbeta signalling after pressure overload. Commun Biol 5(1):1392 |
| abstractText | 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 TGFbeta signalling in heart failure are needed. Here we show that the secreted glycoprotein ADAMTSL3 regulates TGFbeta in the heart. We found that Adamtsl3 knock-out mice develop exacerbated cardiac dysfunction and dilatation with increased mortality, and hearts show increased TGFbeta activity and CFB activation after pressure overload by aortic banding. Further, ADAMTSL3 overexpression in cultured CFBs inhibits TGFbeta signalling, myofibroblast differentiation and collagen synthesis, suggesting a cardioprotective role for ADAMTSL3 by regulating TGFbeta activity and CFB phenotype. These results warrant future investigation of the potential beneficial effects of ADAMTSL3 in heart failure. |
