{"id":"https://openalex.org/W3045503456","doi":"https://doi.org/10.1017/cts.2020.83","title":"4582 NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD) DEPLETION MUST BE SEVERE TO INDUCE CARDIAC DYSFUNCTION AND EVENTUAL FAILURE","display_name":"4582 NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD) DEPLETION MUST BE SEVERE TO INDUCE CARDIAC DYSFUNCTION AND EVENTUAL FAILURE","publication_year":2020,"publication_date":"2020-06-01","ids":{"openalex":"https://openalex.org/W3045503456","doi":"https://doi.org/10.1017/cts.2020.83","mag":"3045503456"},"language":"en","primary_location":{"id":"doi:10.1017/cts.2020.83","doi":"https://doi.org/10.1017/cts.2020.83","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.83","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3185486758AB66A74CC7928BC7034E7F/S2059866120000837a.pdf/div-class-title-4582-nicotinamide-adenine-dinucleotide-nad-depletion-must-be-severe-to-induce-cardiac-dysfunction-and-eventual-failure-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3185486758AB66A74CC7928BC7034E7F/S2059866120000837a.pdf/div-class-title-4582-nicotinamide-adenine-dinucleotide-nad-depletion-must-be-severe-to-induce-cardiac-dysfunction-and-eventual-failure-div.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5084496844","display_name":"Timothy S. Luongo","orcid":"https://orcid.org/0000-0001-7621-7992","observed_orcids":["https://orcid.org/0000-0001-7621-7992"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Timothy Luongo","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Lin Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lin Wang","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036669790","display_name":"Karthikeyani Chellappa","orcid":"https://orcid.org/0000-0001-7397-5974","observed_orcids":["https://orcid.org/0000-0001-7397-5974"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karthikeyani Chellappa","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009535270","display_name":"Melanie R. McReynolds","orcid":"https://orcid.org/0000-0001-5427-2739","observed_orcids":["https://orcid.org/0000-0001-5427-2739"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Melanie R. McReynolds","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5105595657","display_name":"Daniel P. Kelly","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel P. Kelly","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053467552","display_name":"Joshua D. Rabinowitz","orcid":"https://orcid.org/0000-0002-1247-4727","observed_orcids":["https://orcid.org/0000-0002-1247-4727"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joshua D. Rabinowitz","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5008922330","display_name":"Joseph A. Baur","orcid":"https://orcid.org/0000-0001-8262-6549","observed_orcids":["https://orcid.org/0000-0001-8262-6549"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph A. Baur","raw_affiliation_strings":["University of Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I79576946"],"apc_list":{"value":1750,"currency":"USD","value_usd":1750},"apc_paid":{"value":1750,"currency":"USD","value_usd":1750},"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"4","issue":"s1","first_page":"13","last_page":"13"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11051","display_name":"Sirtuins and Resveratrol in Medicine","score":0.9937000274658203,"subfield":{"id":"https://openalex.org/subfields/2717","display_name":"Geriatrics and Gerontology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11051","display_name":"Sirtuins and Resveratrol in Medicine","score":0.9937000274658203,"subfield":{"id":"https://openalex.org/subfields/2717","display_name":"Geriatrics and Gerontology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10821","display_name":"Cardiovascular Function and Risk Factors","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/nad-depletion","display_name":"NAD+ depletion","score":0.921999990940094},{"id":"https://openalex.org/keywords/visfatin","display_name":"visfatin","score":0.9269999861717224},{"id":"https://openalex.org/keywords/heart-failure","display_name":"heart failure","score":0.890999972820282},{"id":"https://openalex.org/keywords/cardiac-dysfunction","display_name":"cardiac dysfunction","score":0.7680000066757202},{"id":"https://openalex.org/keywords/cardiomyocyte-specific-knockout","display_name":"cardiomyocyte-specific knockout","score":0.671999990940094},{"id":"https://openalex.org/keywords/mitochondrial-protein-acetylation","display_name":"mitochondrial protein acetylation","score":0.722000002861023},{"id":"https://openalex.org/keywords/cardiac-hypertrophy","display_name":"cardiac hypertrophy","score":0.7620000243186951},{"id":"https://openalex.org/keywords/left-ventricular-contractility","display_name":"left ventricular contractility","score":0.7390000224113464},{"id":"https://openalex.org/keywords/mitochondrial-oxygen-consumption","display_name":"mitochondrial oxygen consumption","score":0.6489999890327454},{"id":"https://openalex.org/keywords/sirtuin-deacetylase","display_name":"sirtuin deacetylase","score":0.8309999704360962},{"id":"https://openalex.org/keywords/nad-precursors","display_name":"NAD+ precursors","score":0.7440000176429749},{"id":"https://openalex.org/keywords/myocardial-energy-metabolism","display_name":"myocardial energy metabolism","score":0.5070000290870667}],"concepts":[{"id":"https://openalex.org/C75520062","wikidata":"https://www.wikidata.org/wiki/Q15321392","display_name":"NAD+ kinase","level":3,"score":0.9492968320846558},{"id":"https://openalex.org/C2780391879","wikidata":"https://www.wikidata.org/wiki/Q18035058","display_name":"Nicotinamide phosphoribosyltransferase","level":4,"score":0.8132169246673584},{"id":"https://openalex.org/C2776901170","wikidata":"https://www.wikidata.org/wiki/Q12499775","display_name":"Nicotinamide adenine dinucleotide","level":4,"score":0.6916916370391846},{"id":"https://openalex.org/C2780561631","wikidata":"https://www.wikidata.org/wiki/Q421331","display_name":"Sirtuin","level":4,"score":0.6488940715789795},{"id":"https://openalex.org/C2776536020","wikidata":"https://www.wikidata.org/wiki/Q21113719","display_name":"Sirtuin 1","level":4,"score":0.539989709854126},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5104097723960876},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.4819898009300232},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.45884713530540466},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.45334291458129883},{"id":"https://openalex.org/C2779728014","wikidata":"https://www.wikidata.org/wiki/Q192423","display_name":"Nicotinamide","level":3,"score":0.4470920264720917},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4047224819660187},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3695359230041504},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.35875293612480164},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.31012487411499023},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.29301515221595764},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.19161826372146606},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.1017/cts.2020.83","doi":"https://doi.org/10.1017/cts.2020.83","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.83","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3185486758AB66A74CC7928BC7034E7F/S2059866120000837a.pdf/div-class-title-4582-nicotinamide-adenine-dinucleotide-nad-depletion-must-be-severe-to-induce-cardiac-dysfunction-and-eventual-failure-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8846563","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8846563","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Clin Transl Sci","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:dd4c86a7e91d4d6786b941b643a60d7a","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/dd4c86a7e91d4d6786b941b643a60d7a","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Journal of Clinical and Translational Science, Vol 4, Pp 13-13 (2020)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1017/cts.2020.83","doi":"https://doi.org/10.1017/cts.2020.83","is_oa":true,"landing_page_url":"https://doi.org/10.1017/cts.2020.83","pdf_url":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3185486758AB66A74CC7928BC7034E7F/S2059866120000837a.pdf/div-class-title-4582-nicotinamide-adenine-dinucleotide-nad-depletion-must-be-severe-to-induce-cardiac-dysfunction-and-eventual-failure-div.pdf","source":{"id":"https://openalex.org/S4210205013","display_name":"Journal of Clinical and Translational Science","issn_l":"2059-8661","issn":["2059-8661"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","ki-jl-1","poland-20","russia-white-list-2"],"host_organization":"https://openalex.org/P4310311721","host_organization_name":"Cambridge University Press","host_organization_lineage":["https://openalex.org/P4310311721","https://openalex.org/P4310311702"],"host_organization_lineage_names":["Cambridge University Press","University of Cambridge"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical and Translational Science","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3045503456.pdf","grobid_xml":"https://content.openalex.org/works/W3045503456.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2966334389","https://openalex.org/W4400037929","https://openalex.org/W2775095764","https://openalex.org/W3121792663","https://openalex.org/W2920183452","https://openalex.org/W3080230263","https://openalex.org/W7043463448","https://openalex.org/W7135307314","https://openalex.org/W2751396798","https://openalex.org/W4402634263"],"abstract_inverted_index":{"OBJECTIVES/GOALS:":[0],"Nicotinamide":[1,73],"adenine":[2],"dinucleotide":[3],"(NAD)":[4],"plays":[5],"essential":[6],"roles":[7],"in":[8,78,96,148,164,168,185,216,231,273,288],"energy":[9],"metabolism":[10],"and":[11,25,29,64,85,108,125,236,264],"cell":[12],"signaling":[13],"pathways.":[14],"NAD":[15,48,63,91,102,116,170,259,284,305],"functions":[16],"as":[17,51,190,192],"a":[18,52,137,165,182,228,248,267],"coenzyme":[19],"by":[20],"accepting":[21],"electrons":[22],"during":[23],"glycolysis":[24],"the":[26,37,42,65,79,123,196,201,220,295,308],"TCA":[27],"cycle":[28],"subsequently":[30],"donates":[31],"them":[32],"to":[33,159,206,271,299,307],"complex":[34],"I":[35],"of":[36,57,114,127,144,161,199,203,209,233,282,304,310],"electron":[38],"transport":[39],"chain":[40],"providing":[41],"driving":[43],"force":[44],"for":[45,54,71,122,142,155],"ATP":[46],"production.":[47],"also":[49],"acts":[50],"co-substrate":[53],"several":[55,97,222],"classes":[56],"enzymes,":[58],"including":[59],"sirtuin":[60],"deacetylases.":[61],"Both":[62],"enzyme":[66],"that":[67,177,257,294],"is":[68,117],"rate":[69,269],"limiting":[70],"synthesis,":[72],"phosphoribosyltransferase":[74],"(Nampt),":[75],"are":[76],"depleted":[77,265],"failing":[80],"heart,":[81],"concurrent":[82],"with":[83,90],"hyperacetylation":[84],"mitochondrial":[86,234,258],"dysfunction.":[87],"Moreover,":[88],"treatment":[89],"precursors":[92,103],"reduced":[93],"cardiac":[94,193,237,283],"injury":[95],"heart":[98,128,289,296],"failure":[99],"models.":[100],"However,":[101],"may":[104],"have":[105],"systemic":[106],"effects,":[107],"it":[109],"remains":[110],"unproven":[111],"whether":[112],"depletion":[113,281],"myocardial":[115,169],"causative":[118],"or":[119,250],"merely":[120],"correlative":[121],"onset":[124],"progression":[126],"failure.":[129],"METHODS/STUDY":[130],"POPULATION:":[131],"To":[132],"test":[133],"this,":[134],"we":[135,225],"generated":[136],"cardiac-specific":[138],"tamoxifen-inducible":[139],"(\u03b1MHC-MerCreMer)":[140],"model":[141],"deletion":[143,160],"Nampt":[145,178],"(Nampt":[146],"cKO)":[147],"cardiomyocytes.":[149],"Adult":[150],"mice":[151,180,242],"were":[152,261],"administered":[153],"tamoxifen":[154],"5":[156],"days":[157],"leading":[158],"Nampt,":[162],"resulting":[163,215],"72%":[166],"reduction":[167,184],"after":[171],"two-weeks.":[172],"RESULTS/ANTICIPATED":[173],"RESULTS:":[174],"Echocardiography":[175],"revealed":[176],"cKO":[179],"displayed":[181,247],"significant":[183,217],"left":[186],"ventricular":[187],"(LV)":[188],"contractility":[189],"well":[191],"hypertrophy.":[194],"Despite":[195],"further":[197],"loss":[198,303,309],"NAD,":[200],"majority":[202],"animals":[204],"survived":[205],"8":[207,245],"weeks":[208,246],"age":[210],"before":[211],"experiencing":[212],"sudden":[213],"deaths":[214],"mortality":[218],"over":[219],"next":[221],"weeks.":[223],"Remarkably,":[224],"observed":[226],"only":[227],"slight":[229],"increase":[230],"acetylation":[232],"proteins,":[235],"mitochondria":[238],"isolated":[239],"from":[240],"Nampt-null":[241],"even":[243],"at":[244,266],"normal":[249],"higher":[251],"oxygen":[252],"consumption":[253],"rate.":[254],"We":[255],"found":[256],"levels":[260],"preferentially":[262],"maintained":[263],"slower":[268],"compared":[270],"those":[272],"bulk":[274],"tissue.":[275],"DISCUSSION/SIGNIFICANCE":[276],"OF":[277],"IMPACT:":[278],"While":[279],"mild":[280],"has":[285],"been":[286],"reported":[287],"failure,":[290],"our":[291],"data":[292],"indicate":[293],"can":[297],"adapt":[298],"much":[300],"more":[301],"severe":[302],"prior":[306],"viability.":[311]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2020-08-03T00:00:00"}