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PXD033027

PXD033027 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProphylactic or therapeutic NAD+ repletion can prevent or rescue HFpEF, but dietary intervention and weight loss cannot
DescriptionLeft ventricular (LV) diastolic dysfunction is a hallmark of Heart Failure with preserved Ejection Fraction (HFpEF), an escalating global health challenge. We demonstrated selective depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) and the rate-limiting enzyme of the NAD+ biosynthetic salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), in human myocardium with LV diastolic dysfunction. We showed that NAD+ can be replenished in human myocardium with diastolic impairment ex vivo, despite reduced NAMPT expression. In a murine model of HFpEF [a combination exposure to high-fat diet (HFD) and L-NG-Nitro arginine methyl ester (L-NAME)], we compared the benefits of NAD+ precursor supplementation versus dietary intervention. We tested NAD+ repletion by nicotinamide riboside (NR) supplementation using two clinically-relevant strategies: 1) Prophylactic NR repletion before HFpEF onset, and 2) Therapeutic NR repletion after the development of HFpEF. We found that dietary intervention (replacement of HFD and L-NAME with healthy diet) restored myocardial insulin-dependent glucose uptake and glycolysis but did not rescue HFpEF. In contrast, both NAD+ repletion strategies prevented or rescued HFpEF, respectively, plausibly due to restoration of myocardial iron homeostasis, recoupling of glycolysis to the TCA cycle, and upregulation of antioxidant defense.
HostingRepositoryPRIDE
AnnounceDate2024-08-09
AnnouncementXMLSubmission_2024-08-09_04:59:01.082.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMark Larance
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-06 08:57:53ID requested
12024-08-09 04:59:01announced
Publication List
Koay YC, Liu RP, McIntosh B, Vigder N, Lauren S, Bai AY, Tomita S, Li D, Harney D, Hunter B, Zhang Y, Yang J, Bannon P, Philp A, Philp A, Kaye DM, Larance M, Lal S, O'Sullivan JF, Failure. JACC Basic Transl Sci, 9(6):733-750(2024) [pubmed]
10.1016/j.jacbts.2024.01.011;
Keyword List
submitter keyword: mouse, heart
Contact List
Mark Larance
contact affiliationUniversity of Sydney
contact emailmark.larance@sydney.edu.au
lab head
Mark Larance
contact affiliationThe University of Sydney
contact emailmark.larance@sydney.edu.au
dataset submitter
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