PXD036259

PXD036259 is an original dataset announced via ProteomeXchange.

Title	Acetylation and phosphorylation changes to cardiac proteins in experimental HFpEF due to metabolic risk reveal targets for treatment
Description	Aims: Despite the high prevalence of heart failure with preserved ejection fraction (HFpEF), the pathomechanisms remain elusive and specific therapy is lacking. Disease-causing factors include metabolic risk, notably obesity. However, proteomic changes in HFpEF are poorly understood, hampering therapeutic strategies. We sought to elucidate how metabolic syndrome affects cardiac protein expression, phosphorylation and acetylation in the Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 (ZSF1) rat HFpEF model, and to evaluate some changes regarding their potential for treatment. Main methods: ZSF1 obese and lean rats were fed a Purina diet up to the onset of HFpEF in the obese animals. We quantified the proteome, phosphoproteome and acetylome of ZSF1 obese versus lean heart tissues by mass spectrometry and singled out targets for site-specific evaluation. Key findings: We found the acetylome of ZSF1 obese versus lean hearts more severely altered (21% of proteins changed) than the phosphoproteome (9%) or proteome (3%). Proteomic alterations, confirmed by immunoblotting, indicated low-grade systemic inflammation and endothelial remodeling in obese hearts, but low nitric oxide-dependent oxidative/nitrosative stress. Altered acetylation in ZSF1 obese hearts mainly affected pathways important for metabolism, energy production and mechanical function, including hypo-acetylation of mechanical proteins but hyper-acetylation of proteins regulating fatty acid metabolism. Hypo-acetylation and hypo-phosphorylation of elastic titin in ZSF1 obese hearts explained myocardial stiffening. Significance: Cardiometabolic syndrome alters posttranslational modifications, notably acetylation, in experimental HFpEF. Pathway changes implicate a HFpEF signature of low-grade inflammation, endothelial dysfunction, metabolic and mechanical impairment, and suggest titin stiffness and mitochondrial metabolism as promising therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:45.448.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Franziska Koser
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 13:04:02	ID requested
1	2022-10-12 07:20:16	announced
⏵ 2	2023-11-14 08:32:46	announced	2023-11-14: Updated project metadata.

Koser F, Hobbach AJ, Abdellatif M, Herbst V, T, ü, rk C, Reinecke H, Kr, ü, ger M, Sedej S, Linke WA, Acetylation and phosphorylation changes to cardiac proteins in experimental HFpEF due to metabolic risk reveal targets for treatment. Life Sci, 309():120998(2022) [pubmed]

submitter keyword: Diastolic dysfunction

Proteomics

Obesity

Meta-inflammation

Stiffness

Wolfgang A. Linke
contact affiliation	Institue of Physiology II, University of Münster, Münster, Germany
contact email	wlinke@uni-muenster.de
lab head
Franziska Koser
contact affiliation	Institute of Physiology II, University of Münster, Münster
contact email	fkoser@uni-muenster.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036259
     1. Label: PRIDE project
     2. Name: Acetylation and phosphorylation changes to cardiac proteins in experimental HFpEF due to metabolic risk reveal targets for treatment