{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:44:31Z","timestamp":1791211471260,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":242,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010328","name":"Stichting Lijf en Leven","doi-asserted-by":"publisher","award":["60"],"award-info":[{"award-number":["60"]}],"id":[{"id":"10.13039\/501100010328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Persistently unrepaired DNA damage has been identified as a causative factor for vascular ageing. We have previously shown that a defect in the function or expression of the DNA repair endonuclease ERCC1 (excision repair cross complement 1) in mice leads to accelerated, nonatherosclerotic ageing of the vascular system from as early as 8 weeks after birth. Removal of ERCC1 from endothelial alone partly explains this ageing, as shown in endothelial\u2010specific <jats:italic>Ercc1<\/jats:italic> knockout mice. In this study, we determined vascular ageing due to DNA damage in vascular smooth muscle cells, as achieved by smooth muscle\u2010selective genetic removal of ERCC1 DNA repair in mice (SMC\u2010KO: SM22<jats:italic>\u03b1<\/jats:italic>Cre+ <jats:italic>Ercc1<\/jats:italic>fl\/\u2010). Vascular ageing features in SMC\u2010KO and their wild\u2010type littermates (WT: SM22<jats:italic>\u03b1<\/jats:italic>Cre+ <jats:italic>Ercc1<\/jats:italic>fl\/+) were examined at the age of 14 weeks and 25 weeks. Both SMC\u2010KO and WT mice were normotensive. Compared to WT, SMC\u2010KO showed a reduced heart rate, fractional shortening, and cardiac output. SMC\u2010KO showed progressive features of nonatherosclerotic vascular ageing as they aged from 14 to 25 weeks. Decreased subcutaneous microvascular dilatation and increased carotid artery stiffness were observed. Vasodilator responses measured in aortic rings in organ baths showed decreased endothelium\u2010dependent and endothelium\u2010independent responses, mostly due to decreased NO\u2010cGMP signaling. NADPH oxidase 2 and phosphodiesterase 1 inhibition improved dilations. SMC\u2010KO mice showed elevated levels of various cytokines that indicate a balance shift in pro\u2010 and anti\u2010inflammatory pathways. In conclusion, SMC\u2010KO mice showed a progressive vascular ageing phenotype in resistant and conduit arteries that is associated with cardiac remodeling and contractile dysfunction. The changes induced by DNA damage might be limited to VSMC but eventually affect EC\u2010mediated responses. The fact that NADPH oxidase 2 as wells as phosphodiesterase 1 inhibition restores vasodilation suggests that both decreased NO bioavailability and cGMP degradation play a role in local vascular smooth muscle cell ageing induced by DNA damage.<\/jats:p>","DOI":"10.1155\/2021\/2308317","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T19:50:08Z","timestamp":1630439408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Vascular Ageing Features Caused by Selective DNA Damage in Smooth Muscle Cell"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-3890","authenticated-orcid":false,"given":"Ehsan","family":"Ataei Ataabadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-3177","authenticated-orcid":false,"given":"Keivan","family":"Golshiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette","family":"van der Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-2241","authenticated-orcid":false,"given":"Dirk J.","family":"Duncker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-7453","authenticated-orcid":false,"given":"Annika","family":"J\u00fcttner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-1002","authenticated-orcid":false,"given":"Richard","family":"Van Veghel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9368-5779","authenticated-orcid":false,"given":"Ingrid","family":"van der Pluijm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Dutheil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Chalgeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-9553","authenticated-orcid":false,"given":"Robert E.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4749-686X","authenticated-orcid":false,"given":"Gretchen L.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-3585","authenticated-orcid":false,"given":"A. 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