Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8535485 | Life Sciences | 2018 | 8 Pages |
Abstract
First, we found that total elastase activity in an MPS I aorta is elevated. Following that, we demonstrated that CtsB leaks from the lysosome in MPS I human fibroblasts, possibly acting as a degradative agent of extracellular matrix components from the aorta, cardiac muscle, and heart valves. We then used a CtsB inhibitor in vivo in the MPS I mouse model. After 4â¯months of treatment, partial inhibition of CtsB activity in treated mice reduced aortic dilatation, as well as heart valve thickening, and led to improvements in cardiac function parameters, although none of these were completely normalized. Based on these results, we conclude that lysosomal alterations in this disease promote leakage of CtsB to outside the organelle, where this protein can have multiple pathological roles. CtsB inhibition improved cardiovascular parameters in MPS I mice and can have a potential benefit in this disease.
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Authors
Esteban Alberto Gonzalez, Giselle Renata Martins, Angela Maria Vicente Tavares, Michelle Viegas, Edina Poletto, Roberto Giugliani, Ursula Matte, Guilherme Baldo,