{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:47:05Z","timestamp":1782798425533,"version":"3.54.5"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cardiovascular diseases are the leading causes of death and disability worldwide. Their initiation and progression involve multiple complex processes, including metabolic disorders, oxidative stress, inflammatory responses, and cell death. Protein acylation, a rapidly advancing field in post-translational modification research, dynamically regulates protein function, chromatin status, and metabolic signaling networks by covalently attaching various acyl groups to specific protein sites, thereby serving as a key molecular mechanism linking cellular metabolic states to cardiovascular pathology. This review systematically summarizes the mechanisms of protein acylation modifications, including acetylation, lactylation, 2-hydroxyisobutyrylation, and palmitoylation\u2014in major cardiovascular diseases such as cardiac hypertrophy and heart failure, atherosclerosis, myocardial ischemia-reperfusion injury, and arrhythmias. It also provides an overview of recent therapeutic strategies targeting SIRT1, HDACs, acetyl-CoA, Snail1, NLRP3, and Khib-associated metabolic enzymes. Accumulating evidence indicates that maintaining histone acetylation homeostasis, activating SIRT1, inhibiting HDACs, or intervening in specific acylation sites can effectively alleviate myocardial injury, suppress inflammatory responses, and improve cardiac remodeling and repair, offering new insights for mechanistic research and precision therapy of cardiovascular diseases.<\/jats:p>","DOI":"10.3389\/fphar.2026.1866090","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:41:00Z","timestamp":1782798060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The mechanism and treatment of protein acylation modification in cardiovascular disease: a narrative review"],"prefix":"10.3389","volume":"17","author":[{"given":"Kaili","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Management, Hunan Hospital of Integrated Traditional Chinese and Western Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Heilongjiang University of Traditional Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyun","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Medical Management, Hunan Hospital of Integrated Traditional Chinese and Western Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1021\/acs.chemrev.7b00181","article-title":"Lysine acetylation goes global: from epigenetics to metabolism and therapeutics","volume":"118","author":"Ali","year":"2018","journal-title":"Chem. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1073\/pnas.51.5.786","article-title":"Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis","volume":"51","author":"Allfrey","year":"1964","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B3","first-page":"85","article-title":"Cyclophilin D redox-dependent acylation and cardioprotection in ischemia-reperfusion","volume":"36","author":"Amanakis","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"B4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/cvr\/cvaa053","article-title":"Cysteine 202 of cyclophilin D is a site of multiple post-translational modifications and plays a role in cardioprotection","volume":"117","author":"Amanakis","year":"2021","journal-title":"Cardiovasc Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1172\/JCI27438","article-title":"CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy","volume":"116","author":"Backs","year":"2006","journal-title":"J. Clin. Invest."},{"key":"B6","doi-asserted-by":"publisher","first-page":"111162","DOI":"10.1016\/j.biopha.2020.111162","article-title":"HDAC5 inhibition reduces angiotensin II-induced vascular contraction, hypertrophy, and oxidative stress in a mouse model","volume":"134","author":"Bai","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"6559","DOI":"10.3390\/ijms21186559","article-title":"Diabetes mellitus, mitochondrial dysfunction and Ca2+-dependent permeability transition pore","volume":"21","author":"Belosludtsev","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B8","first-page":"1880","article-title":"Sirtuins in the cardiovascular system: potential targets in myocardial ischemia-reperfusion","volume":"128","author":"Bugyei-Twum","year":"2021","journal-title":"Circ. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1152\/physrev.00032.2014","article-title":"The physiology of protein S-acylation","volume":"95","author":"Chamberlain","year":"2015","journal-title":"Physiol. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5876841","DOI":"10.1155\/2021\/5876841","article-title":"SIRT5-Related desuccinylation modification contributes to quercetin-induced protection against heart failure and high-glucose-prompted cardiomyocytes injured through regulation of mitochondrial quality surveillance","volume":"2021","author":"Chang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1074\/mcp.M700021-MCP200","article-title":"Lysine propionylation and butyrylation are novel post-translational modifications in histones","volume":"6","author":"Chen","year":"2007","journal-title":"Mol. Cell Proteomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.gene.2018.07.010","article-title":"Functional genetic variants in the SIRT5 gene promoter in acute myocardial infarction","volume":"675","author":"Chen","year":"2018","journal-title":"Gene"},{"key":"B13","doi-asserted-by":"publisher","first-page":"117384","DOI":"10.1016\/j.biopha.2024.117384","article-title":"Calotropin attenuates ischemic heart failure after myocardial infarction by modulating SIRT1\/FOXD3\/SERCA2a pathway","volume":"179","author":"Chen","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"euaf127","DOI":"10.1093\/europace\/euaf127","article-title":"N-palmitoyl glycine mediates depression-associated atrial fibrillation via Man1a2-dependent autophagy and NRAP dysregulation","volume":"27","author":"Chen","year":"2025","journal-title":"Europace"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1007\/s12265-025-10657-4","article-title":"Acetyl-CoA short-chain Synthetase-2 regulates myocardial ischemia\/reperfusion injury by targeting histone acetylation","volume":"18","author":"Chen","year":"2025","journal-title":"J. Cardiovasc Transl. Res."},{"key":"B16","first-page":"289","article-title":"Astragaloside IV regulates Snail1 lactylation and acetylation to mediate macrophage polarization and improve myocardial infarction","volume":"41","author":"Chen","year":"2025","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"B17","doi-asserted-by":"publisher","first-page":"168163","DOI":"10.1016\/j.bbadis.2026.168163","article-title":"SIRT5 promotes vascular regeneration in peripheral muscle ischemia by regulating malonylation and glycolysis","volume":"1872","author":"Chen","year":"2026","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/nrm3841","article-title":"The growing landscape of lysine acetylation links metabolism and cell signalling","volume":"15","author":"Choudhary","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e30984","DOI":"10.1016\/j.heliyon.2024.e30984","article-title":"Astragaloside IV inhibits angiotensin II-induced atrial fibrosis and atrial fibrillation by SIRT1\/PGC-1\u03b1\/FNDC5 pathway","volume":"10","author":"Cong","year":"2024","journal-title":"Heliyon"},{"key":"B20","first-page":"19","article-title":"Palmitoylation-dependent control of NCX and potassium channel trafficking in cardiac electrophysiology","volume":"119","author":"Congreve","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nchembio.1497","article-title":"Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark","volume":"10","author":"Dai","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jacc.2018.09.086","article-title":"Multitarget strategies to reduce myocardial ischemia\/reperfusion injury: JACC review topic of the week","volume":"73","author":"Davidson","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.cmet.2025.03.006","article-title":"O-GlcNAcylation-mediated endothelial metabolic memory contributes to cardiac damage via small extracellular vesicles","volume":"37","author":"Ding","year":"2025","journal-title":"Cell Metab."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1668718","DOI":"10.3389\/fphar.2025.1668718","article-title":"SIRT1: the first key to unlocking the mystery of cardiovascular diseases","volume":"16","author":"Dinislam","year":"2026","journal-title":"Front. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1161\/CIRCRESAHA.113.300376","article-title":"Cardiac metabolism in heart failure: implications beyond ATP production","volume":"113","author":"Doenst","year":"2013","journal-title":"Circ. Res."},{"key":"B26","first-page":"140586","article-title":"The world of protein acetylation","volume":"1869","author":"Drazic","year":"2021","journal-title":"Biochim. Biophys. Acta Proteins Proteom"},{"key":"B27","first-page":"731","article-title":"O-GlcNAc signaling, sodium channel dysfunction, and diabetic arrhythmias","volume":"2","author":"Erickson","year":"2021","journal-title":"Heart Rhythm O2"},{"key":"B28","first-page":"2107","article-title":"O-GlcNAc signaling modulates GSK-3\u03b2\/NFAT axis and contributes to pressure overload-induced heart failure","volume":"116","author":"Facundo","year":"2020","journal-title":"Cardiovasc Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"175342","DOI":"10.1016\/j.ejphar.2022.175342","article-title":"Resveratrol improves diabetic cardiomyopathy by preventing asymmetric dimethylarginine-caused peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 acetylation","volume":"936","author":"Fang","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1111\/bph.12475","article-title":"Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy","volume":"171","author":"Fillmore","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1016\/j.bbalip.2016.03.020","article-title":"Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes","volume":"1861","author":"Fukushima","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"B32","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1093\/cvr\/cvn215","article-title":"Inhibition of class I histone deacetylase with apicidin attenuates cardiac hypertrophy and failure","volume":"80","author":"Gallo","year":"2008","journal-title":"Cardiovasc Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"105059","DOI":"10.1016\/j.phrs.2020.105059","article-title":"Enhancing PPAR\u03b3 by HDAC inhibition reduces foam cell formation and atherosclerosis in ApoE deficient mice","volume":"160","author":"Gao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1161\/circresaha.123.323160","article-title":"SIRT3 regulates clearance of apoptotic cardiomyocytes by deacetylating frataxin","volume":"133","author":"Gao","year":"2023","journal-title":"Circ. Res."},{"key":"B35","first-page":"879190","article-title":"Role of histone deacetylases in cardiac remodeling and heart failure","volume":"9","author":"Glezeva","year":"2022","journal-title":"Front. Cardiovasc Med."},{"key":"B36","first-page":"741908","article-title":"S-palmitoylation regulates cardiac ion transporters and excitability","volume":"9","author":"G\u00f6k","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e63","DOI":"10.1161\/CIRCRESAHA.118.313865","article-title":"Role of SIRT1 in modulating acetylation of the sarco-endoplasmic reticulum Ca2+-ATPase in heart failure","volume":"124","author":"Gorski","year":"2019","journal-title":"Circ. Res."},{"key":"B38","first-page":"4577","article-title":"Epigenetic regulation of conduction and calcium-handling proteins in arrhythmogenesis","volume":"600","author":"Greener","year":"2022","journal-title":"J. Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"725","DOI":"10.7150\/ijbs.102834","article-title":"Mitochondrial SIRT2-mediated CPT2 deacetylation prevents diabetic cardiomyopathy by impeding cardiac fatty acid oxidation","volume":"21","author":"Guo","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: a neglected therapeutic target","volume":"130","author":"Hausenloy","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1172\/JCI61084","article-title":"HDAC4 controls histone methylation in response to elevated cardiac load","volume":"123","author":"Hohl","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e124079","DOI":"10.1172\/jci.insight.124079","article-title":"The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense","volume":"4","author":"Horton","year":"2019","journal-title":"JCI Insight"},{"key":"B43","doi-asserted-by":"crossref","first-page":"155771","DOI":"10.1016\/j.phymed.2024.155771","article-title":"Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation","volume":"131","author":"Hou","year":"2024","journal-title":"Phytomedicine"},{"key":"B44","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12964-025-02108-z","article-title":"Lysine 2-hydroxyisobutyrylation of HXK1 alters energy metabolism and KATP channel function in the atrium from patients with atrial fibrillation","volume":"23","author":"Hou","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"B45","doi-asserted-by":"publisher","first-page":"6839","DOI":"10.7150\/thno.115402","article-title":"Divergent splicing factor SRSF1 signaling promotes inflammation post-CME: the SRSF1\/ENPP3 axis acts via inhibition of BRD4 O-GlcNAcylation to enhance NF-\u03baB activation and accelerate heart failure","volume":"15","author":"Hu","year":"2025","journal-title":"Theranostics"},{"key":"B46","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.molcel.2018.04.011","article-title":"p300-Mediated lysine 2-Hydroxyisobutyrylation regulates glycolysis","volume":"70","author":"Huang","year":"2018","journal-title":"Mol. Cell"},{"key":"B47","first-page":"100037","article-title":"Landscape and regulation of lysine 2-hydroxyisobutyrylation","volume":"20","author":"Huang","year":"","journal-title":"Mol. Cell Proteomics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"eabe2771","DOI":"10.1126\/sciadv.abe2771","article-title":"The regulatory enzymes and protein substrates for the lysine \u03b2-hydroxybutyrylation pathway","volume":"7","author":"Huang","year":"","journal-title":"Sci. Adv."},{"key":"B49","first-page":"996709","article-title":"Emerging roles of lysine 2-hydroxyisobutyrylation in metabolism and human disease","volume":"10","author":"Huang","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B50","first-page":"2712","article-title":"Beyond ion channels: post-translational control of cardiac excitability and arrhythmia substrates","volume":"117","author":"Hund","year":"2021","journal-title":"Cardiovasc Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1021\/acs.chemrev.6b00750","article-title":"Protein lipidation: occurrence, mechanisms, biological functions, and enabling technologies","volume":"118","author":"Jiang","year":"2018","journal-title":"Chem. Rev."},{"key":"B52","first-page":"21","article-title":"Structure of p300 in complex with acyl-CoA variants reveals the basis of histone acylation specificity","volume":"24","author":"Kaczmarska","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B53","first-page":"1235","article-title":"Sirtuins and NAD^+ in the development and treatment of metabolic and cardiovascular diseases","volume":"127","author":"Kane","year":"2020","journal-title":"Circ. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1911195","DOI":"10.1080\/21688370.2021.1911195","article-title":"HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells","volume":"9","author":"Kashio","year":"2021","journal-title":"Tissue Barriers"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3458","DOI":"10.3390\/cells10123458","article-title":"HOPX plays a critical role in antiretroviral drugs induced epigenetic modification and cardiac hypertrophy","volume":"10","author":"Kashyap","year":"2021","journal-title":"Cells"},{"key":"B56","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"B57","first-page":"686","article-title":"Acetyl-CoA production links metabolic substrate utilization to histone acetylation and cardiac repair after myocardial infarction","volume":"3","author":"Lei","year":"2021","journal-title":"Nat. Metab."},{"key":"B58","first-page":"248","article-title":"Metabolic substrate-driven acetyl-CoA production controls histone acetylation and antioxidant responses in cardiac ischemia-reperfusion","volume":"7","author":"Lei","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"B59","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41580-018-0029-7","article-title":"Regulation of chromatin and gene expression by metabolic enzymes and metabolites","volume":"19","author":"Li","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B60","first-page":"752013","article-title":"Hyperhomocysteinemia promotes atherosclerosis via the HDAC1\/H3K9ac\/miR-34a pathway in macrophage foam cells","volume":"9","author":"Li","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B61","first-page":"694727","article-title":"O-GlcNAcylation and vascular dysfunction: recent advances in inflammation and contractile signaling","volume":"12","author":"Lima","year":"2021","journal-title":"Front. Physiol."},{"key":"B62","first-page":"21677","article-title":"SIRT1 alleviates heart failure by regulating the NF-\u03baB p65\/miR-155\/BDNF signaling pathway","volume":"12","author":"Lin","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B63","doi-asserted-by":"publisher","first-page":"14482","DOI":"10.18632\/aging.103640","article-title":"Sirt1 improves heart failure through modulating the NF-\u03baB p65\/microRNA-155\/BNDF signaling Cascade","volume":"13","author":"Lin","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B64","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/nrm2084","article-title":"Palmitoylation: policing protein stability and traffic","volume":"8","author":"Linder","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"32288","DOI":"10.1074\/jbc.M109.045856","article-title":"Identification and characterization of propionylation at histone H3 lysine 23 in Mammalian cells","volume":"284","author":"Liu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B66","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3892\/mmr.2023.12926","article-title":"KCNQ1OT1 promotes cholesterol accumulation and atherosclerosis progression through the miR-452-3p\/HDAC3\/ABCA1 pathway","volume":"27","author":"Liu","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s42003-024-06086-9","article-title":"STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-\u03b2-catenin axis","volume":"7","author":"Liu","year":"2024","journal-title":"Commun. Biol."},{"key":"B68","first-page":"103171","article-title":"Nat10-dependent RNA acetylation exacerbates ferroptosis and cardiac ischemia-reperfusion injury through the Mybbp1a\/p53 axis","volume":"72","author":"Liu","year":"2024","journal-title":"Redox Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1089\/ars.2021.0190","article-title":"Manganese-induced oxidative stress contributes to intestinal lipid deposition via the deacetylation of PPAR\u03b3 at K339 by SIRT1","volume":"37","author":"Lv","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"B70","doi-asserted-by":"publisher","first-page":"a018762","DOI":"10.1101\/cshperspect.a018762","article-title":"Writers and readers of histone acetylation: structure, mechanism, and inhibition","volume":"14","author":"Marmorstein","year":"2022","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B71","first-page":"e41","article-title":"Heart disease and stroke statistics: a report of US and global data from the American heart association","volume":"151","author":"Martin","year":"2025","journal-title":"Circulation"},{"key":"B72","first-page":"79","article-title":"Targeting inflammation in heart failure with histone deacetylase inhibitors","volume":"27","author":"McKinsey","year":"2021","journal-title":"Mol. Med."},{"key":"B73","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.tig.2004.02.002","article-title":"Cardiac histone acetylation\u2013therapeutic opportunities abound","volume":"20","author":"McKinsey","year":"2004","journal-title":"Trends Genet."},{"key":"B74","first-page":"610","article-title":"Class I and II histone deacetylase inhibitors modulate therapeutic properties of dilated heart tissue-derived mesenchymal stromal cells","volume":"12","author":"Mik\u0161i\u016bnas","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"B75","doi-asserted-by":"publisher","first-page":"277","DOI":"10.19852\/j.cnki.jtcm.20231018.001","article-title":"Gehua jiejiu dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study","volume":"44","author":"Min","year":"2024","journal-title":"J. Tradit. Chin. Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"ra34","DOI":"10.1126\/scisignal.aad5736","article-title":"Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression","volume":"9","author":"Morales","year":"2016","journal-title":"Sci. Signal"},{"key":"B77","first-page":"731","article-title":"Epigenetic and post-translational mechanisms in cardiac arrhythmias","volume":"20","author":"Mu\u00f1oz","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"B78","first-page":"449","article-title":"Comprehensive quantification of fuel use by the failing and nonfailing human heart","volume":"2","author":"Murashige","year":"2020","journal-title":"Nat. Metab."},{"key":"B79","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41580-018-0081-3","article-title":"Functions and mechanisms of non-histone protein acetylation","volume":"20","author":"Narita","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41419-022-05516-y","article-title":"Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-Induced cardiac hypertrophy","volume":"13","author":"Ni","year":"2022","journal-title":"Cell Death Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s00395-013-0361-1","article-title":"Epigenetics: a new mechanism of regulation of heart failure?","volume":"108","author":"Papait","year":"2013","journal-title":"Basic Res. Cardiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.molcel.2013.06.001","article-title":"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways","volume":"50","author":"Park","year":"2013","journal-title":"Mol. Cell"},{"key":"B83","first-page":"87","article-title":"Hyper-O-GlcNAcylation promotes diabetic arrhythmogenesis through Nav1.5 dysfunction and calcium mishandling","volume":"23","author":"Pei","year":"2024","journal-title":"Cardiovasc Diabetol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"M111.012658","DOI":"10.1074\/mcp.M111.012658","article-title":"The first identification of lysine malonylation substrates and its regulatory enzyme","volume":"10","author":"Peng","year":"2011","journal-title":"Mol. Cell Proteomics"},{"key":"B85","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cmet.2015.05.014","article-title":"Acetyl coenzyme A: a central metabolite and second messenger","volume":"21","author":"Pietrocola","year":"2015","journal-title":"Cell Metab."},{"key":"B86","first-page":"H1608","article-title":"SIRT3 deficiency exacerbates ischemia-reperfusion injury: implication for aging hearts","volume":"320","author":"Porter","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"10224","DOI":"10.1111\/jcmm.16959","article-title":"Downregulation of p300\/CBP-associated factor inhibits cardiomyocyte apoptosis via suppression of NF-\u03baB pathway in ischaemia\/reperfusion injury rats","volume":"25","author":"Qiu","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"B88","first-page":"38225","article-title":"Dynamic regulation of GATA4 by histone acetyltransferase p300 in cardiomyocytes","volume":"285","author":"Rai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B89","first-page":"216","article-title":"O-linked GlcNAc modification of HDAC4 protects the diabetic heart from failure","volume":"129","author":"Ramirez-Correa","year":"2021","journal-title":"Circ. Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.freeradbiomed.2022.12.007","article-title":"Eugenol attenuates ischemia-mediated oxidative stress in cardiomyocytes via acetylation of histone at H3K27","volume":"194","author":"Randhawa","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"B91","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.cmet.2013.11.013","article-title":"SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks","volume":"18","author":"Rardin","year":"2013","journal-title":"Cell Metab."},{"key":"B92","doi-asserted-by":"publisher","first-page":"107841","DOI":"10.1016\/j.intimp.2021.107841","article-title":"Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1\/NF-\u03baB pathway","volume":"98","author":"Ren","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.plipres.2016.05.002","article-title":"Fatty acylation of proteins: the long and the short of it","volume":"63","author":"Resh","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"B94","first-page":"2020","article-title":"The SR-mitochondria interaction and mitochondrial permeability transition pore in cardiac ischemia-reperfusion injury","volume":"116","author":"Ruiz-Meana","year":"2020","journal-title":"Cardiovasc Res."},{"key":"B95","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nrm.2016.140","article-title":"Metabolic regulation of gene expression through histone acylations","volume":"18","author":"Sabari","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B96","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.molcel.2018.01.013","article-title":"Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation","volume":"69","author":"Sabari","year":"2018","journal-title":"Mol. Cell"},{"key":"B97","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ceb.2015.02.003","article-title":"Acetyl-CoA and the regulation of metabolism: mechanisms and consequences","volume":"63","author":"Shi","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41467-017-01384-9","article-title":"Characterization of histone acylations links chromatin modifications with metabolism","volume":"8","author":"Simithy","year":"2017","journal-title":"Nat. Commun."},{"key":"B99","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.cmet.2017.09.023","article-title":"Abrogating mitochondrial dynamics in mouse hearts accelerates mitochondrial senescence","volume":"26","author":"Song","year":"2017","journal-title":"Cell Metab."},{"key":"B100","first-page":"1","article-title":"The sirtuin family members SIRT1, SIRT3 and SIRT6: their role in vascular biology and atherogenesis","volume":"352","author":"Sosnowska","year":"2022","journal-title":"Atherosclerosis"},{"key":"B101","first-page":"1297","article-title":"NAA10 dysfunction causes arrhythmia, cardiomyopathy, and developmental defects through impaired N-terminal acetylation","volume":"30","author":"St\u00f8ve","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.3390\/cells12101428","article-title":"SIRT3 deficiency enhances ferroptosis and promotes cardiac fibrosis via p53 acetylation","volume":"12","author":"Su","year":"2023","journal-title":"Cells"},{"key":"B103","first-page":"5093","article-title":"Nutrient sensing by O-GlcNAcylation coordinates T helper 17 differentiation and inflammatory responses","volume":"11","author":"Swamy","year":"2020","journal-title":"Nat. Commun."},{"key":"B104","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.cell.2011.08.008","article-title":"Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification","volume":"146","author":"Tan","year":"2011","journal-title":"Cell"},{"key":"B105","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cmet.2014.03.014","article-title":"Lysine glutarylation is a protein posttranslational modification regulated by SIRT5","volume":"19","author":"Tan","year":"2014","journal-title":"Cell Metab."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.cmet.2025.04.001","article-title":"Protein O-GlcNAcylation and hexokinase mitochondrial dissociation drive heart failure with preserved ejection fraction","volume":"37","author":"Tatekoshi","year":"2025","journal-title":"Cell Metab."},{"key":"B107","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.jphs.2019.02.008","article-title":"Pretreatment with tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia\/reperfusion injury via AMPK\/SIRT1\/PGC-1 alpha signaling pathway","volume":"139","author":"Tian","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"B108","first-page":"291","article-title":"Flux of the central carbon metabolism gives rise to metabolite damage and non-enzymatic protein acylation","volume":"48","author":"Trefely","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"B109","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1161\/circulationaha.120.051911","article-title":"Excessive O-GlcNAcylation causes heart failure and sudden death","volume":"143","author":"Umapathi","year":"2021","journal-title":"Circulation"},{"key":"B110","doi-asserted-by":"publisher","first-page":"29036","DOI":"10.1074\/jbc.M113.486753","article-title":"Widespread and enzyme-independent N\u03b5-acetylation and N\u03b5-succinylation of proteins in the chemical conditions of the mitochondrial matrix","volume":"288","author":"Wagner","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B111","first-page":"1362","article-title":"Crosstalk between lysine 2-hydroxyisobutyrylation and metabolic enzyme activity: emerging implications for mitochondrial metabolism","volume":"13","author":"Wang","year":"2023","journal-title":"Biomolecules"},{"key":"B112","first-page":"389","article-title":"OGT-Dependent O-GlcNAcylation suppresses necroptosis and mediates sevoflurane postconditioning cardioprotection against ischemia-reperfusion injury","volume":"14","author":"Wang","year":"2023","journal-title":"Cell Death Dis."},{"key":"B113","first-page":"702","article-title":"Loss of SIRT1 promotes age-related atrial fibrillation through acetylation-dependent necroptotic remodeling","volume":"149","author":"Wang","year":"2024","journal-title":"Circulation"},{"key":"B114","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1007\/s11418-025-01911-9","article-title":"Loganin ameliorates left ventricular fibrosis and dysfunction induced by pressure overload via the Sirt1\/AKT\/TGF-\u03b21 signaling pathway","volume":"79","author":"Wang","year":"2025","journal-title":"J. Nat. Med."},{"key":"B115","first-page":"1298","article-title":"Crotonylation in cardiovascular and metabolic disease: from mechanism to potential intervention","volume":"12","author":"Wei","year":"2023","journal-title":"Cells"},{"key":"B116","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.molcel.2013.06.003","article-title":"Acetyl-phosphate is a critical determinant of lysine acetylation in E. coli","volume":"51","author":"Weinert","year":"2013","journal-title":"Mol. Cell"},{"key":"B117","first-page":"694","article-title":"Functional relevance of acetylation and succinylation of mitochondrial proteins in metabolic regulation","volume":"14","author":"Weinert","year":"2015","journal-title":"Mol. Cell Proteomics"},{"key":"B118","doi-asserted-by":"publisher","first-page":"72","DOI":"10.21037\/atm-22-6081","article-title":"Lycium barbarum polysaccharide protects cardiomyocytes from hypoxia\/reoxygenation injury via activation of SIRT3\/CypD signaling","volume":"11","author":"Wu","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"B119","doi-asserted-by":"publisher","first-page":"103184","DOI":"10.1016\/j.redox.2024.103184","article-title":"Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation","volume":"73","author":"Wu","year":"2024","journal-title":"Redox Biol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1161\/strokeaha.121.034850","article-title":"Sirtuin 5-Mediated lysine desuccinylation protects mitochondrial metabolism following subarachnoid hemorrhage in mice","volume":"52","author":"Xiao","year":"2021","journal-title":"Stroke"},{"key":"B121","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.molcel.2016.03.036","article-title":"Metabolic regulation of gene expression by histone lysine \u03b2-hydroxybutyrylation","volume":"62","author":"Xie","year":"2016","journal-title":"Mol. Cell"},{"key":"B122","first-page":"72","article-title":"Histone deacetylase inhibition blunts ischemia\/reperfusion-induced cardiac injury by enhancing antioxidant gene programs","volume":"152","author":"Xie","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1038\/s41598-020-58387-8","article-title":"Islet-1 synergizes with Gcn5 to promote MSC differentiation into cardiomyocytes","volume":"10","author":"Xu","year":"2020","journal-title":"Sci. Rep."},{"key":"B124","first-page":"e53043","article-title":"KAT7 maintains endothelial cell identity and vascular integrity through histone acetylation-dependent VEGFR2 transcription","volume":"22","author":"Xu","year":"2021","journal-title":"EMBO Rep."},{"key":"B125","first-page":"1359708","article-title":"Lysine 2-hydroxyisobutyrylation remodeling links glycolytic metabolism to atrial fibrillation","volume":"11","author":"Xu","year":"2024","journal-title":"Front. Cardiovasc Med."},{"key":"B126","first-page":"166431","article-title":"Protein acetylation in cardiovascular diseases: molecular mechanisms and therapeutic implications","volume":"1868","author":"Yan","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B127","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3724\/abbs.2023277","article-title":"Endoplasmic reticulum stress caused by traumatic injury promotes cardiomyocyte apoptosis through acetylation modification of GRP78","volume":"56","author":"Yan","year":"2024","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"B128","first-page":"1713","article-title":"SIRT6 protects endothelial cells against atherosclerosis by deacetylating Caveolin-1 and inhibiting LDL transcytosis","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"B129","first-page":"707","article-title":"SIRT1 deficiency promotes age-related atrial fibrillation via RIPK1 acetylation-mediated necroptosis","volume":"120","author":"Yang","year":"2024","journal-title":"Cardiovasc Res."},{"key":"B130","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41420-022-00906-9","article-title":"HDAC11 promotes both NLRP3\/caspase-1\/GSDMD and caspase-3\/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells","volume":"8","author":"Yao","year":"2022","journal-title":"Cell Death Discov."},{"key":"B131","first-page":"126","article-title":"Acetyl-CoA metabolism links mitochondrial substrate utilization to epigenetic regulation in cardiac injury","volume":"80","author":"Zhang","year":"2023","journal-title":"Cell Mol. Life Sci."},{"key":"B132","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nchembio.495","article-title":"Identification of lysine succinylation as a new post-translational modification","volume":"7","author":"Zhang","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"B134","first-page":"134","article-title":"Lysine 2-hydroxyisobutyrylation: a new player in diverse cellular processes","volume":"7","author":"Zhang","year":"2021","journal-title":"Cell Death Discov."},{"key":"B135","first-page":"3961","article-title":"HDAC3-mediated deacetylation impairs eNOS activity and endothelial function in vascular disease","volume":"17","author":"Zhang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"B136","first-page":"12","article-title":"OGT-Dependent O-GlcNAcylation of IRF1 regulates macrophage polarization and cardiac remodeling in pressure overload-induced heart failure","volume":"119","author":"Zhang","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"B137","first-page":"21","article-title":"NAT10-mediated ac4C RNA acetylation regulates pyroptosis in myocardial ischemia-reperfusion injury","volume":"119","author":"Zhang","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1126\/science.1179689","article-title":"Regulation of cellular metabolism by protein lysine acetylation","volume":"327","author":"Zhao","year":"2010","journal-title":"Science"},{"key":"B139","first-page":"1892","article-title":"Vascular nitric oxide: beyond eNOS J mol cell cardiol?","volume":"10","author":"Zhao","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"B140","first-page":"611","article-title":"Proteomic landscape of lysine 2-hydroxyisobutyrylation reveals metabolic remodeling in valvular atrial fibrillation","volume":"21","author":"Zhao","year":"2023","journal-title":"J. Transl. Med."},{"key":"B141","first-page":"1568","article-title":"Pyruvate dehydrogenase complex in cardiac metabolic remodeling: from physiology to disease","volume":"25","author":"Zhao","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B142","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/ptr.70188","article-title":"Lithospermic acid improves doxorubicin-induced cardiomyopathy through Sirtuin-3-Mediated deacetylation of p53","volume":"40","author":"Zhao","year":"2026","journal-title":"Phytother. Res."},{"key":"B143","first-page":"712","article-title":"MYST1 promotes vascular smooth muscle cell phenotypic switching and neointimal hyperplasia by stabilizing KLF4 through acetylation","volume":"134","author":"Zhou","year":"2024","journal-title":"Circ. Res."},{"key":"B144","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s13023-023-02896-y","article-title":"HDAC5 inhibition attenuates ventricular remodeling and cardiac dysfunction","volume":"18","author":"Zhu","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"B145","first-page":"111633","article-title":"Vaccarin attenuates septic cardiomyopathy by promoting NLRP3 palmitoylation and inhibiting inflammasome activation","volume":"129","author":"Zhu","year":"2024","journal-title":"Int. Immunopharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1866090\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:41:10Z","timestamp":1782798070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1866090\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":145,"alternative-id":["10.3389\/fphar.2026.1866090"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1866090","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"article-number":"1866090"}}