PXD067367-1

PXD067367 is an original dataset announced via ProteomeXchange.

Title	Thrombospondin 1 Aggravates the Progression of Heart Failuren by Inhibiting Mitophagy
Description	Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure cases, yet its underlying mechanisms remain poorly understood. Recent evidence suggests that mitochondrial dysfunction and impaired mitophagy play pivotal roles in HFpEF pathogenesis. Thrombospondin 1 (Thbs1), a matricellular protein, is implicated in cardiovascular remodeling, but its role in HFpEF has not been elucidated. Here, we demonstrate that Thbs1 expression is significantly elevated in the myocardium of HFpEF mice and that Thbs1 exacerbates cardiac dysfunction by suppressing mitophagy. Using a well-established "two-hit" mouse model (high-fat diet and L-NAME), we show that AAV9-mediated knockdown of Thbs1 alleviates diastolic dysfunction, cardiac fibrosis, and myocardial inflammation. RNA sequencing and proteomics analyses revealed enrichment of the PI3K/Akt/mTOR pathway in HFpEF hearts, which was attenuated by Thbs1 silencing. Mechanistically, Thbs1 knockdown restored autophagic flux, promoted mitochondrial clearance, and improved mitochondrial homeostasis in cardiomyocytes. These findings establish Thbs1 as a key regulator of impaired mitophagy in HFpEF and suggest that targeting Thbs1 may provide a therapeutic avenue for treating this complex syndrome.
HostingRepository	iProX
AnnounceDate	2025-08-15
AnnouncementXML	Submission_2025-12-30_18:45:57.459.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xingpeng Bu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-14 20:28:07	ID requested
⏵ 1	2025-12-30 18:45:57	announced

Dataset with its publication pending

submitter keyword: Thrombospondin 1, Heart failure with preserved ejection fraction, Mitophagy, Cardiac remodeling

Huanzhen Chen
contact affiliation	First Hospital of Shanxi Medical University
contact email	chenhz@sxmu.edu.cn
lab head
Xingpeng Bu
contact affiliation	Shanxi Medical University
contact email	buxingpeng@sxbqeh.com.cn
dataset submitter

iProX dataset URI