{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:22:15Z","timestamp":1788916935277,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T00:00:00Z","timestamp":1563148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1181341"],"award-info":[{"award-number":["1181341"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["FONDEQUIP EQM-120205"],"award-info":[{"award-number":["FONDEQUIP EQM-120205"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiovascular risk associated with fetal growth restriction (FGR) could result from an early impaired vascular function. However, whether this effect results in premature vascular aging has not been addressed. We studied the ex vivo reactivity of carotid and femoral arteries in fetal (near term), adults (eight months-old) and aged (16 months-old) guinea pigs in normal (control) and FGR offspring. Additionally, an epigenetic marker of vascular aging (i.e., LINE-1 DNA methylation) was evaluated in human umbilical artery endothelial cells (HUAEC) from control and FGR subjects. Control guinea pig arteries showed an increased contractile response (KCl-induced) and a progressive impairment of NO-mediated relaxing responses as animals get older. FGR was associated with an initial preserved carotid artery reactivity as well as a later significant impairment in NO-mediated responses. Femoral arteries from FGR fetuses showed an increased contractility but a decreased relaxing response compared with control fetuses, and both responses were impaired in FGR-adults. Finally, FGR-HUAEC showed decreased LINE-1 DNA methylation compared with control-HUAEC. These data suggest that the aging of vascular function occurs by changes in NO-mediated responses, with limited alterations in contractile capacity. Further, these effects are accelerated and imposed at early stages of development in subjects exposed to a suboptimal intrauterine environment.<\/jats:p>","DOI":"10.3390\/ijms20143474","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T02:23:16Z","timestamp":1563243796000},"page":"3474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Premature Vascular Aging in Guinea Pigs Affected by Fetal Growth Restriction"],"prefix":"10.3390","volume":"20","author":[{"given":"Adolfo A.","family":"Paz","sequence":"first","affiliation":[{"name":"Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German A.","family":"Arenas","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile"},{"name":"Programa de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Alameda 340, Santiago 8330024, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Castillo-Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile"},{"name":"Programa de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Alameda 340, Santiago 8330024, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Pe\u00f1aloza","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"C\u00e1ceres-Rojas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Odontol\u00f3gicas, Facultad de Odontolog\u00eda, Universidad de Chile, Sergio Livingstone 943, Independencia 8380492, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Suazo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Odontol\u00f3gicas, Facultad de Odontolog\u00eda, Universidad de Chile, Sergio Livingstone 943, Independencia 8380492, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia 7500922, Santiago, Chile"},{"name":"International Center for Andean Studies (INCAS), Universidad de Chile, Baquedano s\/n, Putre, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-6143","authenticated-orcid":false,"given":"Bernardo J.","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"Executive Summary: Heart Disease and Stroke Statistics\u20142016 Update: A Report From the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/ije\/dys116","article-title":"The placental origins of sudden cardiac death","volume":"41","author":"Barker","year":"2012","journal-title":"Int. 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