期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 13, 期 580, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abd7064
关键词
-
资金
- European Research Area Network on Cardiovascular Diseases (ERA-CVD)
- Austrian Science Fund-FWF [I3301-B31]
- (Agence National de la Recherche-ANR)
- (Bundesministerium fur Bildung und Forschung-BMBF)
- Instituto de Salud Carlos III-ISCIII [AC16/00045]
- (Portuguese Foundation for Science and Technology-FCT)
- European Society of Cardiology
- Austrian Society of Cardiology
- Austrian Science Fund [P27166-B23, I3165, P29328-B26, P27893, P31727]
- BioTechMed-Graz
- Ligue contre le Cancer
- Association pour la recherche sur le cancer (ARC)
- Association Ruban Rose, Canceropole Ile-de-France
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Inserm Transfert
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology [ANR-18-IDEX-0001]
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Ministerio de Ciencia e Innovacion (MCIN) [BIO2017-83640-P]
- Comunidad de Madrid
- BioPersMed Graz
- Austrian Research Promotion Agency FFG (VASCage) [868624]
- Pustertaler Verein zur Pravention von Herz-und Hirngefasserkrankungen
- Assessorat fur Gesundheit, Province of Bolzano, Italy
- Austrian Science Fund (FWF) [P29328, I3165] Funding Source: Austrian Science Fund (FWF)
The study suggests that using nicotinamide to increase NAD(+) can improve cardiac dysfunction in HFpEF patients by enhancing myocardial energy metabolism and directly improving cardiomyocyte function. High intake of naturally occurring NAD(+) precursors is associated with lower blood pressure and reduced risk of cardiac mortality.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据