Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 321, Issue 6, Pages R833-R843Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00211.2021
Keywords
angiotensin-converting enzyme 2; COVID-19; fetal growth restriction; preeclampsia; pregnancy
Categories
Funding
- Australian Commonwealth
- Australian Government Research Training Program Scholarship
- Hunter Medical Research Institute researcher bridging funds
- Australian Research Council Future Fellowship [FT150100179]
- Australian Research Council [FT150100179] Funding Source: Australian Research Council
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ACE2 is a membrane-bound protein that plays a key role in regulating the renin-angiotensin system and protecting tissues from inflammation. Dysregulation of ACE2 may contribute to pregnancy complications such as preeclampsia and fetal growth restriction. Understanding the function of ACE2 is important for developing novel therapies to prevent adverse outcomes in pregnancy.
Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.
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