PXD031084

PXD031084 is an original dataset announced via ProteomeXchange.

Title	Proteomics Couples Electrical Remodeling to Inflammation in a Murine Model of Heart Failure with Sinus Node Dysfunction
Description	In patients with heart failure, concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Here, we acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics and pharmacovigilance data highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in-vivo suppression of galectin-3 in the animal model of heart failure prevented SND. Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:19.716.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Konstantin Kahnert
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-19 08:56:52	ID requested
1	2024-04-25 06:14:19	announced
⏵ 2	2024-10-22 06:37:20	announced	2024-10-22: Updated project metadata.

10.1093/CVR/CVAE054;

submitter keyword: LC-MSMS, Phosphoproteomics, Phosphopeptide enrichment, Q-Exactive HF-X, heart,Mouse, TMT labeling, fractionation, Sinus node, Proteomics, Orbitrap, sinoatrial node

Alicia Lundby
contact affiliation	Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
contact email	alicia.lundby@sund.ku.dk
lab head
Konstantin Kahnert
contact affiliation	Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
contact email	konstantinkahnert@gmail.com
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/2024/04/PXD031084

PRIDE project URI

• PRIDE
  1. PXD031084
     1. Label: PRIDE project
     2. Name: Proteomics Couples Electrical Remodeling to Inflammation in a Murine Model of Heart Failure with Sinus Node Dysfunction