{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:55:11Z","timestamp":1784523311709,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870227"],"award-info":[{"award-number":["81870227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianjin Science and Technology Committee","award":["20JCZDJC00510"],"award-info":[{"award-number":["20JCZDJC00510"]}]},{"name":"Key Medical Program of Tianjin Binhai New Area Health Bureau","award":["2018BWKZ005"],"award-info":[{"award-number":["2018BWKZ005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p\/>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>Perivascular adipose tissue (PVAT) surrounding human internal mammary artery (IMA) possesses anticontractile property. Its function under pathological conditions is barely studied. We previously reported that homocysteine impairs the vasodilator function of IMA through endothelium and smooth muscle-dependent mechanisms. This study investigated the effect of homocysteine on the function of PVAT and the associated mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Residual IMA tissues were collected from patients undergoing coronary artery bypass grafting. Vasoreactivity was studied using myograph. Adiponectin was measured by ELISA. Expressions of adiponectin receptors (AdipoRs), eNOS and p-eNOS were determined by RT-qPCR and Western blot.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Exposure to homocysteine augmented the contractile responses of PVAT-intact IMA to U46619 and potassium chloride, regardless with or without endothelium. Such augmentation was also observed in skeletonized IMA with transferred, homocysteine-exposed PVAT. Homocysteine attenuated the relaxant response of PVAT-intact while endothelium-denuded vessels to acetylcholine. Homocysteine lowered adiponectin content in the PVAT, downregulated the expression of AdipoR1 and AdipoR2 as well as eNOS and p-eNOS in skeletonized IMA. The relaxant response of skeletonized IMA to AdipoR agonist AdipoRon was blunted by homocysteine or eNOS inhibitor, and homocysteine significantly attenuated the inhibitory effect of eNOS inhibitor on AdipoRon-induced relaxation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Homocysteine impairs the anticontractile\/vasorelaxing activity of PVAT surrounding the IMA through inhibiting adiponectin\/AdipoR\/eNOS\/nitric oxide signalling pathway.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejcts\/ezad406","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T02:44:35Z","timestamp":1702089875000},"source":"Crossref","is-referenced-by-count":3,"title":["Homocysteine impairs the anticontractile\/vasorelaxing activity of perivascular adipose tissue surrounding human internal mammary artery"],"prefix":"10.1093","volume":"64","author":[{"given":"Jia-Hui","family":"Wei","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Tao","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-876X","authenticated-orcid":false,"given":"Guo-Wei","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"},{"name":"Department of Surgery, Oregon Health and Science University , Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-4431","authenticated-orcid":false,"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College & Tianjin University , Tianjin, China"},{"name":"Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"key":"2023122005555480500_ezad406-B1","doi-asserted-by":"crossref","first-page":"107459","DOI":"10.1016\/j.carpath.2022.107459","article-title":"The pathobiology of perivascular adipose tissue (PVAT), the fourth layer of the blood vessel wall","volume":"61","author":"Hillock-Watling","year":"2022","journal-title":"Cardiovasc Pathol"},{"key":"2023122005555480500_ezad406-B2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11906-018-0835-5","article-title":"Modulation of vascular reactivity by perivascular adipose tissue (PVAT)","volume":"20","author":"Agabiti-Rosei","year":"2018","journal-title":"Curr Hypertens Rep"},{"key":"2023122005555480500_ezad406-B3","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1161\/ATVBAHA.114.303029","article-title":"Perivascular adipose tissue in vascular function and disease: a review of current research and animal models","volume":"34","author":"Brown","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2023122005555480500_ezad406-B4","doi-asserted-by":"crossref","first-page":"615503","DOI":"10.3389\/fphys.2020.615503","article-title":"Perivascular adipose tissue as an indication, contributor to, and therapeutic target for atherosclerosis","volume":"11","author":"Liu","year":"2020","journal-title":"Front Physiol"},{"key":"2023122005555480500_ezad406-B5","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.3390\/ijms21207698","article-title":"Homocysteine and mitochondria in cardiovascular and cerebrovascular systems","volume":"21","author":"Kaplan","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2023122005555480500_ezad406-B6","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.3390\/ijms22041690","article-title":"Hyperhomocysteinemia and cardiovascular disease: is the adenosinergic system the missing link?","volume":"22","author":"Paganelli","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2023122005555480500_ezad406-B7","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/bph.13988","article-title":"Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug targets","volume":"175","author":"Fu","year":"2018","journal-title":"Br J Pharmacol"},{"key":"2023122005555480500_ezad406-B8","doi-asserted-by":"crossref","first-page":"109758","DOI":"10.1016\/j.biopha.2019.109758","article-title":"New insights into phenotypic switching of VSMCs induced by hyperhomocysteinemia: role of endothelin-1 signaling","volume":"123","author":"Chen","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2023122005555480500_ezad406-B9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.atherosclerosis.2015.07.021","article-title":"ER stress mediates homocysteine-induced endothelial dysfunction: modulation of IKCa and SKCa channels","volume":"242","author":"Wang","year":"2015","journal-title":"Atherosclerosis"},{"key":"2023122005555480500_ezad406-B10","doi-asserted-by":"crossref","first-page":"51462","DOI":"10.18632\/oncotarget.17721","article-title":"Activation of PERK branch of ER stress mediates homocysteine-induced BKCa channel dysfunction in coronary artery via FoxO3a-dependent regulation of atrogin-1","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"2023122005555480500_ezad406-B11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.niox.2018.10.001","article-title":"Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries","volume":"81","author":"Hou","year":"2018","journal-title":"Nitric Oxide"},{"key":"2023122005555480500_ezad406-B12","doi-asserted-by":"crossref","first-page":"625","DOI":"10.21037\/atm-20-6821","article-title":"Homocysteine alters vasoreactivity of human internal mammary artery by affecting the KCa channel family","volume":"9","author":"Sun","year":"2021","journal-title":"Ann Transl Med"},{"key":"2023122005555480500_ezad406-B13","first-page":"309","article-title":"Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery","volume":"64","author":"Malinowski","year":"2013","journal-title":"J Physiol Pharmacol"},{"key":"2023122005555480500_ezad406-B14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.atherosclerosissup.2017.05.042","article-title":"Endothelial function and gene expression in perivascular adipose tissue from internal mammary arteries of obese patients with coronary artery disease","volume":"30","author":"Cybularz","year":"2017","journal-title":"Atheroscler Suppl"},{"key":"2023122005555480500_ezad406-B15","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/cphy.c170046","article-title":"Adiponectin regulation and function","volume":"8","author":"Fang","year":"2018","journal-title":"Compr Physiol"},{"key":"2023122005555480500_ezad406-B16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s12020-022-03111-x","article-title":"Adipokines and coronary artery calcification in incident dialysis participants","volume":"77","author":"Roy","year":"2022","journal-title":"Endocrine"},{"key":"2023122005555480500_ezad406-B17","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1007\/s11239-008-0292-0","article-title":"Effects of serum homocysteine and adiponectin levels on platelet aggregation in untreated patients with essential hypertension","volume":"28","author":"Ekmek\u00e7i","year":"2009","journal-title":"J Thromb Thrombolysis"},{"key":"2023122005555480500_ezad406-B18","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1161\/CIRCULATIONAHA.112.001133","article-title":"Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels","volume":"127","author":"Margaritis","year":"2013","journal-title":"Circulation"},{"key":"2023122005555480500_ezad406-B19","doi-asserted-by":"crossref","first-page":"H786","DOI":"10.1152\/ajpheart.00697.2012","article-title":"Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses","volume":"304","author":"Lynch","year":"2013","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2023122005555480500_ezad406-B20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.2174\/1570161114666151202210128","article-title":"Adiponectin: an endothelium-derived vasoprotective factor?","volume":"14","author":"Shen","year":"2016","journal-title":"Curr Vasc Pharmacol"},{"key":"2023122005555480500_ezad406-B21","doi-asserted-by":"crossref","first-page":"H57","DOI":"10.1152\/ajpheart.00533.2021","article-title":"Vascular endothelial adiponectin signaling across the life span","volume":"322","author":"Cohen","year":"2022","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2023122005555480500_ezad406-B22","doi-asserted-by":"crossref","first-page":"875900","DOI":"10.3389\/fphar.2022.875900","article-title":"Role of adiponectin receptor 1 in promoting nitric oxide-mediated flow-induced dilation in the human microvasculature","volume":"13","author":"Cohen","year":"2022","journal-title":"Front Pharmacol"},{"key":"2023122005555480500_ezad406-B23","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.jtcvs.2015.07.027","article-title":"The no-touch saphenous vein for coronary artery bypass grafting maintains a patency, after 16 years, comparable to the left internal thoracic artery: a randomized trial","volume":"150","author":"Samano","year":"2015","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2023122005555480500_ezad406-B24","doi-asserted-by":"crossref","first-page":"e020637","DOI":"10.1161\/JAHA.120.020637","article-title":"Perivascular adipose tissue is a major source of nitric oxide in saphenous vein grafts harvested via the no-touch technique","volume":"11","author":"Saito","year":"2022","journal-title":"J Am Heart Assoc"},{"key":"2023122005555480500_ezad406-B25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejcts.2007.11.007","article-title":"Perivascular tissue of internal thoracic artery releases potent nitric oxide and prostacyclin-independent anticontractile factor","volume":"33","author":"Malinowski","year":"2008","journal-title":"Eur J Cardiothorac Surg"},{"key":"2023122005555480500_ezad406-B26","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/ejcts\/ezac074","article-title":"Vasorelaxing properties of the perivascular tissue of the human radial artery","volume":"61","author":"Kociszewska","year":"2022","journal-title":"Eur J Cardiothorac Surg"},{"key":"2023122005555480500_ezad406-B27","doi-asserted-by":"crossref","first-page":"e011147","DOI":"10.1161\/JAHA.118.011147","article-title":"Differential phenotypes in perivascular adipose tissue surrounding the internal thoracic artery and diseased coronary artery","volume":"8","author":"Numaguchi","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2023122005555480500_ezad406-B28","first-page":"458","article-title":"Hyperhomocysteinemia predicts the severity of coronary artery disease as determined by the SYNTAX score in patients with acute coronary syndrome","volume":"34","author":"Karadeniz","year":"2018","journal-title":"Acta Cardiol Sin"},{"key":"2023122005555480500_ezad406-B29","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1177\/02184923231156731","article-title":"The association of hyperhomocysteinemia with acute post-operative complications following coronary artery bypass grafting","volume":"31","author":"Panicker","year":"2023","journal-title":"Asian Cardiovasc Thorac Ann"}],"container-title":["European Journal of Cardio-Thoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejcts\/advance-article-pdf\/doi\/10.1093\/ejcts\/ezad406\/54182416\/ezad406.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/64\/6\/ezad406\/54650875\/ezad406.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/64\/6\/ezad406\/54650875\/ezad406.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T05:56:23Z","timestamp":1703051783000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejcts\/article\/doi\/10.1093\/ejcts\/ezad406\/7467061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,1]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ejcts\/ezad406","relation":{},"ISSN":["1873-734X"],"issn-type":[{"value":"1873-734X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12,1]]},"published":{"date-parts":[[2023,12,1]]},"article-number":"ezad406"}}