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Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function

Published online by Cambridge University Press:  10 July 2017

V. Oliveira
Affiliation:
Nephrology Division, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
L. V. de Souza
Affiliation:
Nephrology Division, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
T. Fernandes
Affiliation:
School of Physical Education and Sport, Biochemistry and Molecular Biology Laboratory, University of São Paulo, São Paulo, Brazil
S. D. S. Junior
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
M. H. C. de Carvalho
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
E. H. Akamine
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
L. C. Michelini
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
E. M. de Oliveira
Affiliation:
School of Physical Education and Sport, Biochemistry and Molecular Biology Laboratory, University of São Paulo, São Paulo, Brazil
M. d. C. Franco
Affiliation:
Nephrology Division, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
Corresponding
E-mail address:

Abstract

Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms involved are not fully understood. Emerging evidence has suggested the potential role of endothelial progenitor cells (EPCs) in vascular health and repair. Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and EPCs derived from the peripheral blood (PB) and bone marrow (BM) in vitro. Pregnant Wistar rats were fed an ad libitum diet (control group) or 50% of the ad libitum diet (restricted group) throughout gestation. We determined vascular reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male offspring from both groups (aged: 19–20 weeks). Moreover, the amount, functional capacity, and senescence of EPCs were assessed in vitro. Our results indicated that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was similar between both groups; however, IUGR decreased the functional capacity of EPCs from the PB and BM. Furthermore, the senescence process was accelerated in BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the deleterious changes in EPCs from IUGR rats, such as reduced EPC function and accelerated senescence in vitro. These findings may contribute towards elucidating the possible mechanisms involved in endothelial dysfunction induced by fetal programming.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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