Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease

Cited 3 time in webofscience Cited 0 time in scopus
  • Hit : 216
  • Download : 0
Fabry disease (FD), a lysosomal storage disorder, is caused by defective a-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or pro-gressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling. Fasudil reduced the levels of p-SMAD2 and TSP1 in FD-VECs and increased the expression of angiogenic factors. Furthermore, fasudil downregulated the endothelial-to-mesenchymal transi-tion (EndMT) and mitochondrial function of FD-VECs. Oral administration of fasudil to FD mice alleviated several FD phe-notypes, including LVH, renal fibrosis, anhidrosis, and heat insensitivity. Our findings demonstrate that fasudil is a novel candidate for FD therapy.
Publisher
CELL PRESS
Issue Date
2023-04
Language
English
Article Type
Article
Citation

MOLECULAR THERAPY, v.31, no.4, pp.1002 - 1016

ISSN
1525-0016
DOI
10.1016/j.ymthe.2023.02.003.
URI
http://hdl.handle.net/10203/306897
Appears in Collection
BS-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 3 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0