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PXD019895

PXD019895 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCathepsin A contributes to left ventricular remodeling by degrading the antioxidant enzyme extracellular superoxide dismutase
DescriptionIn the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM-remodeling and left ventricular (LV) dysfunction. This study aimed to evaluate the effects of CatA overexpression on LV remodeling. A proteomic analysis of the secretome of adult mouse cardiac fibroblasts upon digestion by CatA identified the extracellular antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate of CatA (5-fold decreased abundance; p=0.0001). In vitro, cardiomyocytes and cardiac fibroblasts expressed and secreted CatA protein. EC-SOD protein was expressed and secreted only by cardiac fibroblasts. Cardiomyocyte-specific over-expression of CatA and increased activity in the LV of transgenic mice (CatA-TG) reduced EC-SOD protein levels by 43% (p<0.001). Loss of EC-SOD-mediated anti-oxidative protection resulted in accumulation of superoxide radicals (WT: 4.54±1.2 vs. CatA-TG: 8.62±2.3µmol/mg tissue/min; p=0.0012), increased inflammation, myocyte hypertrophy (WT: 19.8±1.0 vs. CatA-TG: 21.9±1.8µm; p=0.024), cellular apoptosis, and elevated mRNA expression of hypertrophy-related and pro-fibrotic marker genes, without effecting intracellular detoxifying proteins. In CatA-TG mice LV interstitial fibrosis formation was enhanced by 19% (p=0.028) and type I/type III collagen ratio was shifted towards higher abundance of collagen I fibers (p=0.026). Cardiac remodeling in CatA-TG was accompanied by increased LV weight/body weight and LV enddiastolic volume (WT: 50.8±5.8 vs. CatA-TG: 61.9±6.2 µl; p=0.018). Thus, in the heart CatA-mediated reduction of EC-SOD protein contributes to increased oxidative stress, myocyte hypertrophy, ECM remodeling and inflammation. This implicates CatA as a potential therapeutic target to prevent ventricular remodeling.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:08:44.173.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD019895
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterXiaoke Yin
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-19 03:05:23ID requested
12020-07-09 22:37:54announced
22024-10-22 05:08:44announced2024-10-22: Updated project metadata.
Publication List
10.6019/PXD019895;
Keyword List
submitter keyword: extracellular matrix protein
oxidative stress, cardiac hypertrophy, cardiac remodeling, extracellular superoxide dismutase,Cathepsin A
carboxypeptidase
Contact List
Manuel Mayr
contact affiliationKing's BHF Centre of Research Excellence, King's College London, London, UK
contact emailmanuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliationCardiovascular Division, King's College London
contact emailxiaoke.yin@kcl.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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