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Open AccessArticle

Premature Vascular Aging in Guinea Pigs Affected by Fetal Growth Restriction

Department of Neonatology, Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago 8330024, Santiago, Chile
Programa de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8330024, Santiago, Chile
Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia 7500922, Santiago, Chile
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Sergio Livingstone 943, Independencia 8380492, Santiago, Chile
International Center for Andean Studies (INCAS), Universidad de Chile, Baquedano s/n, Putre, Chile
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3474;
Received: 31 May 2019 / Revised: 5 July 2019 / Accepted: 13 July 2019 / Published: 15 July 2019
(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)
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. View Full-Text
Keywords: Fetal Growth Restriction; Early Vascular Aging; Cardiovascular Diseases; Endothelial Dysfunction Fetal Growth Restriction; Early Vascular Aging; Cardiovascular Diseases; Endothelial Dysfunction
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MDPI and ACS Style

Paz, A.A.; Arenas, G.A.; Castillo-Galán, S.; Peñaloza, E.; Cáceres-Rojas, G.; Suazo, J.; Herrera, E.A.; Krause, B.J. Premature Vascular Aging in Guinea Pigs Affected by Fetal Growth Restriction. Int. J. Mol. Sci. 2019, 20, 3474.

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