PXD051715-1

PXD051715 is an original dataset announced via ProteomeXchange.

Title	Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice
Description	Abstract: Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and death in the elderly. While aging strongly increases the incidence of HFpEF, the specific influences of aging on HFpEF at molecular and pathophysiological levels remain unclear. Here, we show that aged mice, when subjected to chronic metabolic and hypertensive stress (2-hit stress), develop an aggravated cardiometabolic HFpEF phenotype compared to younger counterparts. Aged HFpEF mice also display unique pathological characteristics reminiscent of those found in HFpEF patients. We demonstrate that age-related dysfunction in protein quality control (PQC) exacerbates proteostatic stress in HFpEF. Specifically, we demonstrate that increased protein synthesis induced by 2-hit stress combines with age-related impairment in protein degradation in aged HFpEF hearts, culminating in the accumulation of protein aggregates. These findings underscore the importance of incorporating aging into preclinical HFpEF models and support the therapeutic potential of targeting PQC mechanisms to ameliorate disease outcomes.
HostingRepository	PRIDE
AnnounceDate	2025-01-10
AnnouncementXML	Submission_2025-01-10_03:56:34.063.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051715
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ricard Rodriguez-Mias
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-24 13:27:20	ID requested
⏵ 1	2025-01-10 03:56:34	announced

10.1016/J.JACBTS.2024.11.006;

10.6019/PXD051715;

submitter keyword: HFpEF,heart failure, protein quality control, protein degradation, cardiac aging, proteostasis, protein synthesis

Judit Villen
contact affiliation	Department of Genome Sciences, University of Washington, Seattle, WA, USA
contact email	jvillen@uw.edu
lab head
Ricard Rodriguez-Mias
contact affiliation	University of Washington
contact email	rr65@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051715
     1. Label: PRIDE project
     2. Name: Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice