{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:44:35Z","timestamp":1768506275046,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,26]]},"group-title":"Biochemistry","reference-count":18,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,29]]},"abstract":"<jats:title>Introductory Paragraph<\/jats:title>\n                <jats:p>Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored. Moreover, the cardioprotective properties of ketones in preclinical RVF are unknown. Here, we show a compensatory ketosis is absent in pulmonary arterial hypertension (PAH) patients with RVF. In the monocrotaline (MCT) rat model of PAH-mediated RVF, a dietary-induced ketosis improves RV function, suppresses NLRP3 inflammasome activation, and combats RV fibrosis. The summation of these data suggest ketogenic therapies may be particularly efficacious in RVF, and therefore future studies evaluating ketogenic interventions in human RVF are warranted.<\/jats:p>","DOI":"10.1101\/2023.04.26.538410","type":"posted-content","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T01:40:14Z","timestamp":1682559614000},"source":"Crossref","is-referenced-by-count":2,"title":["Ketone Bodies in Right Ventricular Failure: A Unique Therapeutic Opportunity"],"prefix":"10.64898","author":[{"given":"Madelyn","family":"Blake","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrycja","family":"Puchalska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Kazmirczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thenappan","family":"Thenappan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-6742","authenticated-orcid":false,"given":"Kurt W.","family":"Prins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023070403501386000_2023.04.26.538410v2.1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1056\/NEJMra2207410","article-title":"Right Ventricular Failure","volume":"388","year":"2023","journal-title":"N Engl J Med"},{"key":"2023070403501386000_2023.04.26.538410v2.2","first-page":"e876","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","year":"2022","journal-title":"Circulation"},{"key":"2023070403501386000_2023.04.26.538410v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.07.011"},{"key":"2023070403501386000_2023.04.26.538410v2.4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022362"},{"key":"2023070403501386000_2023.04.26.538410v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.022"},{"key":"2023070403501386000_2023.04.26.538410v2.6","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1161\/CIRCRESAHA.123.321872","article-title":"Ketones and the Heart: Metabolic Principles and Therapeutic Implications","volume":"132","year":"2023","journal-title":"Circ Res"},{"key":"2023070403501386000_2023.04.26.538410v2.7","doi-asserted-by":"crossref","unstructured":"Lopaschuk, GD , Dyck, JRB . Ketones and the cardiovascular system. Nat Cardiovasc Res 2023, 425\u2013437.","DOI":"10.1038\/s44161-023-00259-1"},{"key":"2023070403501386000_2023.04.26.538410v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3804"},{"key":"2023070403501386000_2023.04.26.538410v2.9","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202110-2274OC"},{"key":"2023070403501386000_2023.04.26.538410v2.10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017355"},{"key":"2023070403501386000_2023.04.26.538410v2.11","doi-asserted-by":"crossref","unstructured":"Song JP , Chen L , Chen X , Ren J , Zhang NN , Tirasawasdichai T , Hu ZL , Hua W , Hu YR , Tang HR , Chen HV , Hu SS . Elevated plasma \u03b2-hydroxybutyrate predicts adverse outcomes and disease progression in patients with arrhythmogenic cardiomyopathy. Sci Transl Med 2020; 12.","DOI":"10.1126\/scitranslmed.aay8329"},{"key":"2023070403501386000_2023.04.26.538410v2.12","first-page":"2045894019890553","article-title":"Plasma metabolomic profile in chronic thromboembolic pulmonary hypertension","volume":"10","year":"2020","journal-title":"Pulm Circ"},{"key":"2023070403501386000_2023.04.26.538410v2.13","doi-asserted-by":"crossref","first-page":"e028232","DOI":"10.1161\/JAHA.122.028232","article-title":"Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension","volume":"12","year":"2023","journal-title":"J Am Heart Assoc"},{"key":"2023070403501386000_2023.04.26.538410v2.14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jacbts.2022.12.001","article-title":"Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules","volume":"8","year":"2023","journal-title":"JACC Basic Transl Sci"},{"key":"2023070403501386000_2023.04.26.538410v2.15","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s44161-022-00113-w","article-title":"Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension","volume":"1","year":"2022","journal-title":"Nature Cardiovascular Research"},{"key":"2023070403501386000_2023.04.26.538410v2.16","doi-asserted-by":"crossref","first-page":"122048","DOI":"10.1016\/j.talanta.2020.122048","article-title":"Determination of ketone bodies in biological samples via rapid UPLC-MS\/MS","volume":"225","year":"2021","journal-title":"Talanta"},{"key":"2023070403501386000_2023.04.26.538410v2.17","doi-asserted-by":"crossref","unstructured":"Prins KW , Tian L , Wu D , Thenappan T , Metzger JM , Archer SL . Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension. J Am Heart Assoc 2017;6.","DOI":"10.1161\/JAHA.117.006195"},{"key":"2023070403501386000_2023.04.26.538410v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2021.09.004"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.04.26.538410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:35:36Z","timestamp":1768451736000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.04.26.538410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":18,"URL":"https:\/\/doi.org\/10.1101\/2023.04.26.538410","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.heliyon.2023.e22227","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,4,26]]},"subtype":"preprint"}}