PXD033027

PXD033027 is an original dataset announced via ProteomeXchange.

Title	Prophylactic or therapeutic NAD+ repletion can prevent or rescue HFpEF, but dietary intervention and weight loss cannot
Description	Left 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.
HostingRepository	PRIDE
AnnounceDate	2024-08-09
AnnouncementXML	Submission_2024-08-09_04:59:01.082.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Larance
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-06 08:57:53	ID requested
⏵ 1	2024-08-09 04:59:01	announced

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;

submitter keyword: mouse, heart

Mark Larance
contact affiliation	University of Sydney
contact email	mark.larance@sydney.edu.au
lab head
Mark Larance
contact affiliation	The University of Sydney
contact email	mark.larance@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033027
     1. Label: PRIDE project
     2. Name: Prophylactic or therapeutic NAD+ repletion can prevent or rescue HFpEF, but dietary intervention and weight loss cannot