PXD058715

PXD058715 is an original dataset announced via ProteomeXchange.

Title	Cardiac Amyloid Tissue Proteome
Description	Cardiac AL and ATTR are potentially fatal cardiomyopathies. Current therapies do not address mechanisms of tissue dysfunction, mostly because these remain unknown. Our prior work has focused on the amyloid plaque proteome, which may not capture tissue-wide proteomic alterations. In this study, we used a bulk (entire biopsy) tissue proteomics approach to evaluate mechanisms of tissue dysfunction in cardiac AL/ATTR. We included 76 ATTR cases and 27 AL cases. In stage 3 AL patients, pathways involved in coagulation, extracellular matrix (ECM) remodeling, epithelial-to-mesenchymal transition (EMT), complement activation, hypoxia and clathrin-mediated endocytosis were increased compared to stage 1/2,whereas pathways involved in healthy cardiac metabolism and proteostasis were decreased. In Mayo stage 2/3 ATTR, immunoglobulin proteins, complement and keratin pathways were increased compared to stage 1. Principal component analyses identified an ATTR group with worse survival independent of existing staging systems that also showed upregulation of complement and downregulation of oxidative phosphorylation pathways. Finally, when comparing AL with ATTR, complement proteins were increased in ATTR whereas clathrin-mediated endocytosis , mRNA splicing, spliceosome pathways and ribosomal proteins were increased in AL. Clathrin-mediated endocytosis has been implicated in Aβ amyloid clearance by non-immune cells in the setting of Alzheimer’s disease and could represent a proteostatic mechanism of cardiomyocytes in response to AL fibrils. Impaired spliceosome and translation machinery has been associated with cardiac ECM-R in other cardiomyopathies. Our results support an immune-mediated mechanism of tissue toxicity in cardiac amyloidosis including activation of the complement cascade, especially among ATTR patients with worse outcomes.
HostingRepository	PRIDE
AnnounceDate	2025-01-16
AnnouncementXML	Submission_2025-01-15_20:54:30.406.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Surendra Dasari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-09 20:35:40	ID requested
⏵ 1	2025-01-15 20:54:31	announced

10.1080/13506129.2024.2448440;

Netzel BC, Charlesworth MC, Johnson KL, French AJ, Dispenzieri A, Maleszewski JJ, McPhail ED, Grogan M, Redfield MM, Weivoda M, Muchtar E, Gertz MA, Kumar SK, Misra P, Vrana J, Theis J, Hayman SR, Ramirez-Alvarado M, Dasari S, Kourelis T, Whole tissue proteomic analyses of cardiac ATTR and AL unveil mechanisms of tissue damage. Amyloid, 32(1):72-80(2025) [pubmed]

submitter keyword: ATTR,cardiac amyloid, AL

Surendra Dasari
contact affiliation	Mayo Clinic, Rochester, MN
contact email	dasari.surendra@mayo.edu
lab head
Surendra Dasari
contact affiliation	Mayo Clinic
contact email	dasari.surendra@mayo.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD058715

PRIDE project URI

• PRIDE
  1. PXD058715
     1. Label: PRIDE project
     2. Name: Cardiac Amyloid Tissue Proteome