In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 15, No. 688 ( 2023-03-22)
Abstract:
Arrhythmogenic cardiomyopathy (ACM) is a debilitating disease with clear genetic links but variable penetrance and poorly understood mechanisms. Here Tsui and colleagues analyzed heart tissue from patients with ACM along with inducible pluripotent stem cell–derived cardiomyocytes and mice carrying a plakophilin-2 ( Pkp2 ) mutation to reveal that decreased expression of desmosomal and adherens junction proteins correlated with cardiac dysfunction and fibrosis. Proteomics data indicated involvement of the ubiquitin-proteasome system (UPS) in the degradation of these proteins, and inhibition of the UPS improved protein expression and calcium dynamics in isolated mutant cardiomyocytes. These results suggest that therapies aimed at increasing stability of desmosomal proteins may improve cardiac function in patients with ACM.--AW
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.add4248
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
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