20.500.12556/DKUM-89686 Nicotinamide for the treatment of heart failure with preserved ejection fraction Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans. heart failure hypertension niacinamide metabolic syndrome srčno popuščanje hipertenzija niacinamid presnovni sindrom true false true American Association for the Advancement of Science Angleški jezik Slovenski jezik Znanstveno delo 2024-08-05 11:57:11 2024-08-06 11:29:46 2024-08-07 03:41:20 0000-00-00 00:00:00 2021 0 0 Str. 1-15 Št. 580 Letn. 13 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2020-07-18 2021-01-12 2021-02-10 616.12 159472131 10.1126/scitranslmed.abd7064 1946-6242 Abdellatif-2021-Nicotinamide_for_the_treatment.pdf Abdellatif-2021-Nicotinamide_for_the_treatment.pdf 1 09AB91CF86C1F6F0B74EFF2B671213EA 6cfde3d5747c95eea29bb7002eeae81bdfc1aeaf000d110de7033e1e130b84ea 70d1a397-5315-11ef-a033-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=182013 https://www.science.org/doi/10.1126/scitranslmed.abd7064?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 1 285ee65c-5311-11ef-a033-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=182009 Medicinska fakulteta 0 0 0