PXD055401

PXD055401 is an original dataset announced via ProteomeXchange.

Title	Pharmacological inhibition of the glucocorticoid regenerating enzyme 11ßhydroxysteroid dehydrogenase type 1 after myocardial infarction preserves cardiac function in a translational pig model
Description	Background and Purpose: Adrenal glucocorticoids (GC) increase acutely after myocardial infarction (MI) and thereafter tissue levels are maintained selectively within cells expressing the enzyme 11ßHydroxysteroid Dehydrogenase type 1 (11ßHSD1) that regenerates active GC from circulating metabolites. GC initially protect cardiomyocytes and prevent excessive inflammation after MI but can also suppress subsequent wound repair leading to functional decline. The present study aimed to investigate the potential of pharmacological 11ßHSD1inhibition after MI to prevent deterioration of cardiac function. Experimental Approach: Oral 11ßHSD1 inhibitor AZD8329, or vehicle, were administered from 48h to 28 days after ischaemia/reperfusion in a translational pig model concurrently receiving clinically relevant therapeutic intervention (statin, anti-platelet, ACE inhibitor and ß adrenoreceptor antagonist). Key Results: AZD8329 treatment resulted in increased plasma accumulation of cortisone substrate consistent with successful 11ßHSD1 inhibition. Gd enhanced MRI showed equivalent infarct size in both groups prior to commencing treatment. 28 days after MI cardiac function and LV area were preserved in the AZD8329 treated group relative to vehicle. There was no impact of 11ßHSD1 inhibitor on neovascularisation or infarct area compared to vehicle. However, mass spectrometry imaging revealed AZD8329 binding to the healing infarct and altered regulation of extracellular matrix processing was highlighted by birefringence microscopy and proteomic analysis. Conclusions and Implications: Pharmacological inhibition of 11ßHSD1 after MI prevents deterioration of cardiac function and detrimental remodelling. 11ßHSD1 inhibitors have safely reached phase 2 in clinical trials and could be repurposed for use after MI/reperfusion to prevent the development of heart failure.
HostingRepository	PRIDE
AnnounceDate	2026-01-15
AnnouncementXML	Submission_2026-01-15_07:34:42.783.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von Kriegsheim
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: NEWT:9825;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-30 15:36:35	ID requested
⏵ 1	2026-01-15 07:34:43	announced

10.1111/bph.70297;

Al Disi S, Ascione R, Khan S, Johnson T, Sammut E, Bruno VD, Baz Lopez D, James CA, Simpson J, Homer NZ, Millar M, Singh T, von Kreigsheim A, Mills NL, Walker BR, Andrew R, Webster SP, Whittaker A, Freeman A, Gray GA, HSD1) after myocardial infarction preserves cardiac function in a translational mini-pig model. Br J Pharmacol, ():(2025) [pubmed]

submitter keyword: heart, pig

Gillian Gray
contact affiliation	university of Edinburgh
contact email	Gillian.Gray@ed.ac.uk
lab head
Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ed.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/01/PXD055401

PRIDE project URI

• PRIDE
  1. PXD055401
     1. Label: PRIDE project
     2. Name: Pharmacological inhibition of the glucocorticoid regenerating enzyme 11ßhydroxysteroid dehydrogenase type 1 after myocardial infarction preserves cardiac function in a translational pig model