PXD021957
PXD021957 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Heart failure, lysine acetylation, mitochondria, inflammation, ketone body, fatty acid uptake |
Contact List
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 |
Full Dataset Link List
iProX dataset URI |