{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:54:12Z","timestamp":1788440052858,"version":"build-2803163510"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,5,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Myxomatous mitral valve disease (MMVD), a naturally occurring heart disease, affects 10% to 15% of the canine population. Canine MMVD shares many similarities with human MMVD. Untargeted metabolomics was performed to identify changes in metabolic pathways and biomarkers with potential clinical utilities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Serum samples from 27 healthy, 22 stage B1, 18 stage B2 preclinical MMVD dogs, and 17 MMVD dogs with a history of congestive heart failure (CHF) were analyzed. Linear regression analysis identified 173 known metabolites whose concentrations were different among the 4 groups (adjusted\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), of which 40% belonged to amino acid super pathways, while 30% were lipids. More than 50% of significant metabolites were correlated with left atrial diameter but not left ventricular dimension. Acylcarnitines, tricarboxylic acid cycle intermediates, and creatine accumulated in proportion to MMVD severity. \u03b1\u2010Ketobutyrate and ketone bodies were increased as MMVD advanced. Nicotinamide, a key substrate of the main nicotinamide adenine dinucleotide (NAD\n              <jats:sup>+<\/jats:sup>\n              ) salvage pathway, was decreased, while quinolinate of the de novo NAD\n              <jats:sup>+<\/jats:sup>\n              biosynthesis was increased in CHF dogs versus healthy dogs. 3\u2010Methylhistidine, marker for myofibrillar protein degradation, was higher in CHF dogs than non\u2010CHF dogs. Trimethylamine N\u2010oxide (TMAO) and TMAO\u2013producing precursors, including carnitine, phosphatidylcholine, betaine, and trimethyllysine, were increased in CHF dogs versus non\u2010CHF dogs. Elevated levels of uremic toxins, including guanidino compounds, TMAO, and urea, were observed in CHF dogs. Pathway analysis highlighted the importance of bioenergetics and amino acid metabolism in canine MMVD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our study revealed altered energy metabolism, amino acid metabolic programming, and reduced renal function in the development of MMVD and CHF. Complex interplays along the heart\u2010kidney\u2010gut axis were implicated.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.018923","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T20:01:29Z","timestamp":1624305689000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Metabolomics Analysis Reveals Deranged Energy Metabolism and Amino Acid Metabolic Reprogramming in Dogs With Myxomatous Mitral Valve Disease"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-6024","authenticated-orcid":false,"given":"Qinghong","family":"Li","sequence":"first","affiliation":[{"name":"Nestl\u00e9 Purina Research St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-8374","authenticated-orcid":false,"given":"\u00c9va","family":"Larouche\u2010Lebel","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry A.","family":"Loughran","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry P.","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan S.","family":"Suchodolski","sequence":"additional","affiliation":[{"name":"Gastrointestinal Laboratory Department of Small Animal Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-9226","authenticated-orcid":false,"given":"Mark A.","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine School of Veterinary Medicine University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvc.2012.01.011"},{"key":"e_1_3_2_3_2","first-page":"457","volume-title":"Textbook of Canine and Feline Cardiology","author":"Buchanan J","year":"1999","unstructured":"Buchanan J. 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