کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8535485 1560532 2018 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cathepsin B inhibition attenuates cardiovascular pathology in mucopolysaccharidosis I mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Cathepsin B inhibition attenuates cardiovascular pathology in mucopolysaccharidosis I mice
چکیده انگلیسی
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 4 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 196, 1 March 2018, Pages 102-109
نویسندگان
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