{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:44:35Z","timestamp":1794023075021,"version":"4.8.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-120732"],"award-info":[{"award-number":["HL-120732"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-128215"],"award-info":[{"award-number":["HL-128215"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-126012"],"award-info":[{"award-number":["HL-126012"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-147933"],"award-info":[{"award-number":["HL-147933"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-155765"],"award-info":[{"award-number":["HL-155765"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,5,28]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. We recently demonstrated in mice that a combination of metabolic and hypertensive stress recapitulates key features of human HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Using this novel preclinical HFpEF model, we set out to define and manipulate metabolic dysregulations occurring in HFpEF myocardium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      We observed impairment in mitochondrial fatty acid oxidation associated with hyperacetylation of key enzymes in the pathway. Downregulation of sirtuin 3 and deficiency of NAD\n                      <jats:sup>+<\/jats:sup>\n                      secondary to an impaired NAD\n                      <jats:sup>+<\/jats:sup>\n                      salvage pathway contribute to this mitochondrial protein hyperacetylation. Impaired expression of genes involved in NAD\n                      <jats:sup>+<\/jats:sup>\n                      biosynthesis was confirmed in cardiac tissue from patients with HFpEF. Supplementing HFpEF mice with nicotinamide riboside or a direct activator of NAD\n                      <jats:sup>+<\/jats:sup>\n                      biosynthesis led to improvement in mitochondrial function and amelioration of the HFpEF phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Collectively, these studies demonstrate that HFpEF is associated with myocardial mitochondrial dysfunction and unveil NAD\n                      <jats:sup>+<\/jats:sup>\n                      repletion as a promising therapeutic approach in the syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.120.317046","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T05:01:39Z","timestamp":1619067699000},"page":"1629-1641","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":248,"title":["NAD\n                    <sup>+<\/sup>\n                    Repletion Reverses Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3551-2861","authenticated-orcid":true,"given":"Dan","family":"Tong","sequence":"first","affiliation":[{"name":"Internal Medicine (Cardiology) (D.T., G.G.S., N.J., F.A., P.A.S., A.E., H.Y., L.I.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-7171","authenticated-orcid":true,"given":"Gabriele 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