{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:00:22Z","timestamp":1794006022296,"version":"4.8.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sino-Swiss Science and Technology Cooperation","award":["IZLCZ0_206081\/1"],"award-info":[{"award-number":["IZLCZ0_206081\/1"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82161138026"],"award-info":[{"award-number":["82161138026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss National Research Science Foundation","award":["SNF 310030_166576\/1"],"award-info":[{"award-number":["SNF 310030_166576\/1"]}]},{"name":"Foundation for Cardiovascular Research\u2014Zurich Heart House"},{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Enhancing SIRT1 activity exerts beneficial cardiovascular effects. In diabetes, plasma SIRT1 levels are reduced. We aimed to investigate the therapeutic potential of chronic recombinant murine SIRT1 (rmSIRT1) supplementation to alleviate endothelial and vascular dysfunction in diabetic mice (db\/db).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Left internal mammary arteries obtained from patients undergoing coronary artery bypass grafting with or without a diagnosis of diabetes were assayed for SIRT1 protein levels. Twelve-week-old male db\/db mice and db\/+ controls were treated with vehicle or rmSIRT1 intraperitoneally for 4 weeks, after which carotid artery pulse wave velocity (PWV) and energy expenditure\/activity were assessed by ultrasound and metabolic cages, respectively. Aorta, carotid, and mesenteric arteries were isolated to determine endothelial and vascular function using the myograph system.<\/jats:p>\n                  <jats:p>Arteries obtained from diabetic patients had significantly lower levels of SIRT1 relative to non-diabetics. In line, aortic SIRT1 levels were reduced in db\/db mice compared to db\/+ mice, while rmSIRT1 supplementation restored SIRT1 levels. Mice receiving rmSIRT1 supplementation displayed increased physical activity and improved vascular compliance as reflected by reduced PWV and attenuated collagen deposition. Aorta of rmSIRT1-treated mice exhibited increased endothelial nitric oxide (eNOS) activity, while endothelium-dependent contractions of their carotid arteries were significantly decreased, with mesenteric resistance arteries showing preserved hyperpolarization. Ex vivo incubation with reactive oxygen species (ROS) scavenger Tiron and NADPH oxidase inhibitor apocynin revealed that rmSIRT1 leads to preserved vascular function by suppressing NADPH oxidase (NOX)-related ROS synthesis. Chronic rmSIRT1 treatment resulted in reduced expression of both NOX1 and NOX4, in line with a reduction in aortic protein carbonylation and plasma nitrotyrosine levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In diabetic conditions, arterial SIRT1 levels are significantly reduced. Chronic rmSIRT1 supplementation improves endothelial function and vascular compliance by enhancing eNOS activity and suppressing NOX-related oxidative stress. Thus, SIRT1 supplementation may represent novel therapeutic strategy to prevent diabetic vascular disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad102","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T12:09:22Z","timestamp":1688472562000},"page":"2190-2201","source":"Crossref","is-referenced-by-count":52,"title":["Chronic SIRT1 supplementation in diabetic mice improves endothelial function by suppressing oxidative stress"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8826-1330","authenticated-orcid":false,"given":"Kangmin","family":"Yang","sequence":"first","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Wagistrasse 12, 8952 Schlieren , 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetiana","family":"Lapikova-Bryhinska","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Wagistrasse 12, 8952 Schlieren , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin O","family":"Schmiady","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University Heart Center, University Hospital Zurich , R\u00e4mistrasse 100, 8091 Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong , Sassoon Road 21, Pok Fu Lam, 000000 Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiluo","family":"Geng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong , Sassoon Road 21, Pok Fu Lam, 000000 Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni G","family":"Camici","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"Department of Research and Education, University Hospital Zurich , R\u00e4mistrasse 100, 8091 Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-033X","authenticated-orcid":false,"given":"Aimin","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong , Sassoon Road 21, Pok Fu Lam, 000000 Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"L\u00fcscher","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Wagistrasse 12, 8952 Schlieren , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"2023101619462052300_cvad102-B1","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1161\/CIRCRESAHA.118.313865","article-title":"Role of SIRT1 in modulating acetylation of the sarco-endoplasmic reticulum Ca(2+)-ATPase in heart failure","volume":"124","author":"Gorski","year":"2019","journal-title":"Circ 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