PXD021957

PXD021957 is an original dataset announced via ProteomeXchange.

Title	Targeting mitochondria-inflammation circuit by β-hydroxybutyrate mitigates heart failure with preserved ejection fraction
Description	Rationale: Over 50% of heart failure patients have preserved, rather than reduced ejection fraction (HFpEF vs. HFrEF). Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model. Methods and Results: By combining the age, long-term high-fat diet and desoxycorticosterone pivalate challenge in a mouse model we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of interleukin (IL)-1β/IL-18, and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate (β-OHB) level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokines-triggered mitochondrial dysfunction and fibrosis. Moreover, β-OHB downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of citrate synthase and inhibition of fatty acid uptake. Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis which can be ameliorated by promoting β-OHB abundance.
HostingRepository	iProX
AnnounceDate	2021-10-22
AnnouncementXML	Submission_2023-08-24_21:08:10.683.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yan Deng
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-13 19:04:05	ID requested
1	2021-05-12 20:41:46	announced
⏵ 2	2023-08-24 21:08:11	announced	2023-08-25: Update publication information.

Deng Y, Xie M, Li Q, Xu X, Ou W, Zhang Y, Xiao H, Yu H, Zheng Y, Liang Y, Jiang C, Chen G, Du D, Zheng W, Wang S, Gong M, Chen Y, Tian R, Li T, -Hydroxybutyrate Mitigates HFpEF. Circ Res, 128(2):232-245(2021) [pubmed]

submitter keyword: Heart failure, lysine acetylation, mitochondria, inflammation, ketone body, fatty acid uptake

Tao Li
contact affiliation	West China Hospital, Sichuan University
contact email	scutaoli1981@scu.edu.edu
lab head
Yan Deng
contact affiliation	Sichuan University
contact email	dengyan19900304@163.com
dataset submitter

iProX dataset URI