{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:40:33Z","timestamp":1789072833532,"version":"build-2803163510"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600384"],"award-info":[{"award-number":["81600384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470595"],"award-info":[{"award-number":["81470595"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003345","name":"Chinese Academy of Meteorological Sciences","doi-asserted-by":"publisher","award":["2019-I2M-5\\u2013055"],"award-info":[{"award-number":["2019-I2M-5\\u2013055"]}],"id":[{"id":"10.13039\/501100003345","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Hebei Provincial Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.ejphar.2021.174012","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T15:22:20Z","timestamp":1615648940000},"page":"174012","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["\u03b2-Hydroxybutyrate inhibits cardiac microvascular collagen 4 accumulation by attenuating oxidative stress in streptozotocin-induced diabetic rats and high glucose treated cells"],"prefix":"10.1016","volume":"899","author":[{"given":"Huanli","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsheng","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.ejphar.2021.174012_bib1","doi-asserted-by":"crossref","first-page":"165739","DOI":"10.1016\/j.bbadis.2020.165739","article-title":"Cardiac ketone body metabolism","volume":"1866","author":"Abdul Kadir","year":"2020","journal-title":"Biochim. Biophys. Acta. Mol. Basis. Dis."},{"issue":"9","key":"10.1016\/j.ejphar.2021.174012_bib2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11886-020-01349-3","article-title":"Heart failure with preserved ejection fraction-a concise review","volume":"22","author":"Adamczak","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"10.1016\/j.ejphar.2021.174012_bib3","first-page":"6890501","article-title":"MicroRNA and microvascular complications of diabetes","author":"Barutta","year":"2018","journal-title":"Int. J. Endocrinol. 2018"},{"issue":"3","key":"10.1016\/j.ejphar.2021.174012_bib4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.celrep.2018.09.058","article-title":"Salt-responsive metabolite, \u03b2-hydroxybutyrate, attenuates hypertension","volume":"25","author":"Chakraborty","year":"2018","journal-title":"Cell Rep."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2174\/1874609810666170315112634","article-title":"Protein tyrosine nitration: role in aging","volume":"10","author":"Chakravarti","year":"2017","journal-title":"Curr. Aging Sci."},{"issue":"5","key":"10.1016\/j.ejphar.2021.174012_bib6","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.cell.2019.07.048","article-title":"Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet","volume":"178","author":"Cheng","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2021.174012_bib7","first-page":"7387128","article-title":"The significance of an increased beta-hydroxybutyrate at presentation to the emergency department in patients with diabetes in the absence of a hyperglycemic emergency","author":"Depczynski","year":"2019","journal-title":"J. Diabetes. Res. 2019"},{"key":"10.1016\/j.ejphar.2021.174012_bib8","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.omtn.2020.02.001","article-title":"Osteopontin upregulates Col IV expression by repressing miR-29a in human retinal capillary endothelial cells","volume":"20","author":"Duan","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"6","key":"10.1016\/j.ejphar.2021.174012_bib9","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.molcel.2018.07.036","article-title":"\u03b2-Hydroxybutyrate prevents vascular senescence through hnRNP A1-mediated upregulation of Oct4","volume":"71","author":"Han","year":"2018","journal-title":"Mol. Cell."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib10","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s12276-020-0415-z","article-title":"\u03b2-Hydroxybutyrate and its metabolic effects on age-associated pathology","volume":"52","author":"Han","year":"2020","journal-title":"Exp. Mol. Med."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174012_bib11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10741-020-09921-3","article-title":"Insulin resistance and heart failure during treatment with sodium glucose cotransporter 2 inhibitors: proposed role of ketone utilization","volume":"25","author":"Hattori","year":"2020","journal-title":"Heart Fail. Rev."},{"key":"10.1016\/j.ejphar.2021.174012_bib12","doi-asserted-by":"crossref","first-page":"173376","DOI":"10.1016\/j.ejphar.2020.173376","article-title":"Role of AMP-activated protein kinase on cardio-metabolic abnormalities in the development of diabetic cardiomyopathy: a molecular landscape","volume":"888","author":"Haye","year":"2020","journal-title":"Eur. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib13","doi-asserted-by":"crossref","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."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174012_bib14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1530\/EJE-19-0710","article-title":"Effects of \u03b2-hydroxybutyrate on cognition in patients with type 2 diabetes","volume":"182","author":"Jensen","year":"2020","journal-title":"Eur. J. Endocrinol."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib15","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","article-title":"Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity","volume":"122","author":"Jia","year":"2018","journal-title":"Circ. Res."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib16","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/jdi.13009","article-title":"Canagliflozin, a sodium-glucose cotransporter 2 inhibitor, normalizes renal susceptibility to type 1 cardiorenal syndrome through reduction of renal oxidative stress in diabetic rats","volume":"10","author":"Kimura","year":"2019","journal-title":"J Diabetes. Investig."},{"issue":"1","key":"10.1016\/j.ejphar.2021.174012_bib17","doi-asserted-by":"crossref","DOI":"10.1111\/eci.13036","article-title":"The copper-zinc superoxide dismutase activity in selected diseases","volume":"49","author":"Lewandowski","year":"2019","journal-title":"Eur. J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2021.174012_bib18","doi-asserted-by":"crossref","DOI":"10.1177\/1533317519883496","article-title":"\u03b2-Hydroxybutyrate ameliorates A\u03b2-induced downregulation of TrkA expression by inhibiting HDAC1\/3 in SH-SY5Y cells","volume":"35","author":"Li","year":"2020","journal-title":"Am. J. Alzheimers. Dis. Other. Demen."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2021.174012_bib19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2013.02.015","article-title":"Protein nitration promotes inducible nitric oxide synthase transcription mediated by NF-\u03baB in high glucose-stimulated human lens epithelial cells","volume":"370","author":"Li","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"issue":"1","key":"10.1016\/j.ejphar.2021.174012_bib20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1530\/JME-18-0009","article-title":"C-peptide prevents SMAD3 binding to alpha promoters to inhibit collagen type IV synthesis","volume":"61","author":"Li","year":"2018","journal-title":"J. Mol. Endocrinol."},{"issue":"12","key":"10.1016\/j.ejphar.2021.174012_bib21","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1007\/s00592-020-01552-2","article-title":"Up-regulation of MMP-2 by histone H3K9 \u03b2-hydroxybutyrylation to antagonize glomerulosclerosis in diabetic rat","volume":"57","author":"Luo","year":"2020","journal-title":"Acta Diabetol."},{"issue":"8","key":"10.1016\/j.ejphar.2021.174012_bib22","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/ar.23567","article-title":"Basement membrane Type IV collagen and laminin: an overview of their biology and value as fibrosis biomarkers of liver disease","volume":"300","author":"Mak","year":"2017","journal-title":"Anat. Rec."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174012_bib23","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/advances\/nmz104","article-title":"Utility of ketone supplementation to enhance physical performance: a systematic review","volume":"11","author":"Margolis","year":"2020","journal-title":"Adv. Nutr."},{"key":"10.1016\/j.ejphar.2021.174012_bib24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","article-title":"\u03b2-Hydroxybutyrate: a signaling metabolite","volume":"37","author":"Newman","year":"2017","journal-title":"Annu. Rev. Nutr."},{"issue":"18","key":"10.1016\/j.ejphar.2021.174012_bib25","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1161\/CIRCULATIONAHA.118.036459","article-title":"Cardiovascular effects of treatment with the ketone body 3-hydroxybutyrate in chronic heart failure patients","volume":"139","author":"Nielsen","year":"2019","journal-title":"Circulation"},{"issue":"2","key":"10.1016\/j.ejphar.2021.174012_bib26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/ejhf.1646","article-title":"Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment","volume":"22","author":"Packer","year":"2020","journal-title":"Eur. J. Heart Fail."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174012_bib27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/met.2014.0101","article-title":"Effect of hyperketonemia (Acetoacetate) on nuclear factor-\u03baB and p38 mitogen-activated protein kinase activation mediated intercellular adhesion molecule 1 upregulation in endothelial cells","volume":"13","author":"Rains","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"issue":"8","key":"10.1016\/j.ejphar.2021.174012_bib28","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.cellsig.2016.04.005","article-title":"\u03b2-Hydroxybutyrate: a signaling metabolite in starvation response?","volume":"28","author":"Rojas-Morales","year":"2016","journal-title":"Cell. Signal."},{"key":"10.1016\/j.ejphar.2021.174012_bib29","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.15092","article-title":"Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body \u03b2-hydroxybutyrate","volume":"5","author":"Sleiman","year":"2016","journal-title":"Elife"},{"issue":"1","key":"10.1016\/j.ejphar.2021.174012_bib30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1042\/BST20190240","article-title":"Why a d-\u03b2-hydroxybutyrate monoester?","volume":"48","author":"Soto-Mota","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.ejphar.2021.174012_bib31","doi-asserted-by":"crossref","first-page":"104506","DOI":"10.1016\/j.yrtph.2019.104506","article-title":"Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults","volume":"109","author":"Soto-Mota","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174012_bib32","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cmet.2019.07.016","article-title":"Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans","volume":"30","author":"Stekovic","year":"2019","journal-title":"Cell Metabol."},{"key":"10.1016\/j.ejphar.2021.174012_bib33","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3389\/fphys.2017.00848","article-title":"On the metabolism of exogenous ketones in humans","volume":"8","author":"Stubbs","year":"2017","journal-title":"Front. Physiol."},{"issue":"1","key":"10.1016\/j.ejphar.2021.174012_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0211005","article-title":"The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome","volume":"14","author":"Trotta","year":"2019","journal-title":"PloS One"},{"issue":"12","key":"10.1016\/j.ejphar.2021.174012_bib35","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.117.004417","article-title":"Cardiac-specific Bdh1 overexpression ameliorates oxidative stress and cardiac remodeling in pressure overload-induced heart failure","volume":"10","author":"Uchihashi","year":"2017","journal-title":"Circ. Heart. Fail."},{"issue":"5","key":"10.1016\/j.ejphar.2021.174012_bib36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/iub.1627","article-title":"Ketone bodies mimic the life span extending properties of caloric restriction","volume":"69","author":"Veech","year":"2017","journal-title":"IUBMB Life"},{"issue":"1","key":"10.1016\/j.ejphar.2021.174012_bib37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12933-018-0754-4","article-title":"Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving 'SIRT1 and PGC-1\u03b1","volume":"17","author":"Waldman","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"issue":"7","key":"10.1016\/j.ejphar.2021.174012_bib38","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/ajh\/hpaa024","article-title":"Cinnamaldehyde ameliorates vascular dysfunction in diabetic mice by activating Nrf2","volume":"33","author":"Wang","year":"2020","journal-title":"Am. J. Hypertens."},{"key":"10.1016\/j.ejphar.2021.174012_bib39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuroscience.2017.09.056","article-title":"Ketogenic metabolism inhibits histone deacetylase (HDAC) and reduces oxidative stress after spinal cord injury in rats","volume":"366","author":"Wang","year":"2017","journal-title":"Neuroscience"},{"issue":"4","key":"10.1016\/j.ejphar.2021.174012_bib40","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1136\/heartjnl-2017-311448","article-title":"Reactive oxygen species signalling in the diabetic heart: emerging prospect for therapeutic targeting","volume":"104","author":"Wilson","year":"2018","journal-title":"Heart"},{"key":"10.1016\/j.ejphar.2021.174012_bib41","doi-asserted-by":"crossref","first-page":"101345","DOI":"10.1016\/j.tice.2020.101345","article-title":"\u03b2-hydroxybutyrate antagonizes aortic endothelial injury by promoting generation of VEGF in diabetic rats","volume":"64","author":"Wu","year":"2020","journal-title":"Tissue Cell"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921001655?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921001655?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:06:57Z","timestamp":1777406817000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921001655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":41,"alternative-id":["S0014299921001655"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174012","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"\u03b2-Hydroxybutyrate inhibits cardiac microvascular collagen 4 accumulation by attenuating oxidative stress in streptozotocin-induced diabetic rats and high glucose treated cells","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"174012"}}