10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Nicotinamide for the treatment of heart failure with preserved ejection fraction

      1 , 1 , 2 , 3 , 4 , 1 , 5 , 5 , 2 , 1 , 6 , 7 , 1 , 8 , 9 , 3 , 4 , 7 , 10 , 10 , 1 , 11 , 1 , 1 , 6 , 12 , 12 , 13 , 14 , 10 , 1 , 11 , 1 , 1 , 1 , 1 , 1 , 6 , 15 , 12 , 8 , 9 , 6 , 13 , 6 , 10 , 6 , 10 , 6 , 13 , 14 , 5 , 5 , 7 , 16 , 17 , 2 , 3 , 4 , 18 , 19 , 20 , 1 , 6 , 21
      Science Translational Medicine
      American Association for the Advancement of Science (AAAS)

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references62

          • Record: found
          • Abstract: found
          • Article: not found

          Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

          Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Andromeda: a peptide search engine integrated into the MaxQuant environment.

            A key step in mass spectrometry (MS)-based proteomics is the identification of peptides in sequence databases by their fragmentation spectra. Here we describe Andromeda, a novel peptide search engine using a probabilistic scoring model. On proteome data, Andromeda performs as well as Mascot, a widely used commercial search engine, as judged by sensitivity and specificity analysis based on target decoy searches. Furthermore, it can handle data with arbitrarily high fragment mass accuracy, is able to assign and score complex patterns of post-translational modifications, such as highly phosphorylated peptides, and accommodates extremely large databases. The algorithms of Andromeda are provided. Andromeda can function independently or as an integrated search engine of the widely used MaxQuant computational proteomics platform and both are freely available at www.maxquant.org. The combination enables analysis of large data sets in a simple analysis workflow on a desktop computer. For searching individual spectra Andromeda is also accessible via a web server. We demonstrate the flexibility of the system by implementing the capability to identify cofragmented peptides, significantly improving the total number of identified peptides.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis

                Bookmark

                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Science Translational Medicine
                Sci. Transl. Med.
                American Association for the Advancement of Science (AAAS)
                1946-6234
                1946-6242
                February 10 2021
                February 10 2021
                February 10 2021
                February 10 2021
                : 13
                : 580
                : eabd7064
                Affiliations
                [1 ]Department of Cardiology, Medical University of Graz, Graz 8036, Austria.
                [2 ]Institute of Physiology II, University of Münster, Münster 48149, Germany.
                [3 ]Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif 94805, France.
                [4 ]Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris 75006, France.
                [5 ]Department of Surgery and Physiology, Cardiovascular Research and Development Centre (UnIC), Faculty of Medicine, University of Porto, Porto 4200-319, Portugal.
                [6 ]BioTechMed Graz, Graz 8010, Austria.
                [7 ]Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
                [8 ]Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne 50931, Germany.
                [9 ]Center for Molecular Medicine (CMMC), University of Cologne, Cologne 50931, Germany.
                [10 ]Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz 8010, Austria.
                [11 ]Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz 8010, Austria.
                [12 ]Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover 30625, Germany.
                [13 ]Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz 8010, Austria.
                [14 ]Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz 8010, Austria.
                [15 ]Leibniz Institute on Aging, Jena 07745, Germany.
                [16 ]Department of Neurology, Medical University of Innsbruck, Innsbruck 6020, Austria.
                [17 ]VASCage, Research Centre for Promoting Vascular Health in the Ageing Community, Innsbruck 6020, Austria.
                [18 ]Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris 75015, France.
                [19 ]Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou 215000, China.
                [20 ]Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Solna 17164, Sweden.
                [21 ]Faculty of Medicine, University of Maribor, Maribor 2000, Slovenia.
                Article
                10.1126/scitranslmed.abd7064
                33568522
                1577846a-f5c3-4a41-889f-6d6f2d8b570d
                © 2021

                https://www.sciencemag.org/about/science-licenses-journal-article-reuse

                History

                Comments

                Comment on this article