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Clin Sci (Lond). 2019 Jan 8;133(1):55-74. doi: 10.1042/CS20171550. Print 2019 Jan 15.

Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data.

South AM1,2,3,4, Shaltout HA3,5,6,4,7, Washburn LK1,3,4, Hendricks AS3,4, Diz DI3,4,7, Chappell MC8,4,7.

Author information

1
Department of Pediatrics, Section of Nephrology, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
2
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
3
Cardiovascular Sciences Center, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
4
Hypertension and Vascular Research, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
5
Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
6
Department of Pharmacology and Toxicology, School of Pharmacy, University of Alexandria, Egypt.
7
Department of Surgery, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.
8
Cardiovascular Sciences Center, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A. mchappel@wakehealth.edu.

Abstract

Hypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin-angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (AT1R) axis. The emerging view of alternative pathways within the RAS that may functionally antagonize the Ang II axis raise the possibility that programming events also target the non-classical components of the RAS as an additional mechanism contributing to the development and progression of hypertension. In the current review, we evaluate the potential role of the ACE2-Ang-(1-7)-Mas receptor (MasR) axis of the RAS in fetal programming events and cardiovascular and renal dysfunction. Specifically, the review examines the impact of fetal programming on the Ang-(1-7) axis within the circulation, kidney, and brain such that the loss of Ang-(1-7) expression or tone, contributes to the chronic dysregulation of blood pressure (BP) and cardiometabolic disease in the offspring, as well as the influence of sex on potential programming of this pathway.

KEYWORDS:

ACE; angiotensin converting enzyme 2; angiotensin-(1-7); fetal programming

PMID:
30622158
PMCID:
PMC6716381
DOI:
10.1042/CS20171550
[Indexed for MEDLINE]
Free PMC Article

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