Renin-angiotensin system in normal pregnancy and in preeclampsia: A comprehensive review

Leal, Caio Ribeiro Vieira; Costa, Larissa Braga; Ferreira, Guilherme Costa; Ferreira, Alexandre de Melo; Reis, Fernando M.; Silva, Ana Cristina Simões e

doi:10.1016/j.preghy.2022.01.011

Cited by 32 publications

(19 citation statements)

References 61 publications

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“…Alongside the lung, the placenta is another major extra-renal RAS activity site. Placental RAS has been reported to play an important role in the pathogenesis of preeclampsia (preE), a multisystem, pregnancy-specific disorder [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection

Giardini

Ornaghi

Gambacorti‐Passerini

et al. 2022

Viruses

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COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38–85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

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Section: Introductionmentioning

confidence: 99%

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection

Giardini

Ornaghi

Gambacorti‐Passerini

et al. 2022

Viruses

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“…Contradictory reports are available regarding the roles of RAS components in PE pathophysiology. Compared with uncomplicated pregnancies, humans and experimental studies showed that while PE is often associated with diminished blood renin and Ang II, vascular expression of AT1 receptors as well as vasoconstrictor and inflammatory actions of Ang II are exaggerated 23 – 26 . Moreover, published data on ACE activity and expression during PE are contradictory 26 .…”

Section: Introductionmentioning

confidence: 99%

“…with uncomplicated pregnancies, humans and experimental studies showed that while PE is often associated with diminished blood renin and Ang II, vascular expression of AT1 receptors as well as vasoconstrictor and inflammatory actions of Ang II are exaggerated [23][24][25][26] . Moreover, published data on ACE activity and expression during PE are contradictory 26 . Alternatively, Ang1-7 signaling is depressed over the course of PE 27 and gestational Ang1-7 supplementation ameliorates the PE-related hypertension, inflammation, and oxidative stress through the upregulation of peroxisome proliferator-activated receptors gamma 28 .…”

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confidence: 99%

The renin-angiotensin system modulates endotoxic postconditioning of exacerbated renal vasoconstriction in preeclamptic offspring

Morgaan

Sallam

El‐Gowelli

et al. 2023

Sci Rep

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We recently reported exacerbated endotoxic signs of neuroinflammation and autonomic defects in offspring of preeclamptic (PE) dams. Here, we investigated whether PE programming similarly modifies hemodynamic and renal vasoconstrictor responsiveness to endotoxemia in PE offspring and whether this interaction is modulated by gestational angiotensin 1–7 (Ang1-7). Preeclampsia was induced by gestational treatment with L-NAME. Adult offspring was challenged with lipopolysaccharides (LPS, 5 mg/kg) and systolic blood pressure (SBP) and renal vasoconstrictions were assessed 4 h later. Male, but not female, offspring of PE rats exhibited SBP elevations that were blunted by LPS. Renal vasoconstrictions induced by angiotensin II (Ang II), but not phenylephrine, were intensified in perfused kidneys of either sex. LPS blunted the heightened Ang II responses in male, but not female, kidneys. While renal expressions of AT1-receptors and angiotensin converting enzyme (ACE) were increased in PE offspring of both sexes, ACE2 was upregulated in female offspring only. These molecular effects were diminished by LPS in male offspring. Gestational Ang1-7 caused sex-unrelated attenuation of phenylephrine vasoconstrictions and preferentially downregulated Ang II responses and AT1-receptor and nuclear factor-kB (NFkB) expressions in females. Together, endotoxemia and Ang1-7 offset in sexually-related manners imbalances in renal vasoconstriction and AT1/ACE/ACE2 signaling in PE offspring.

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“…In the gastrointestinal system, the RAS regulates intestinal physiological functions including electrolyte homeostasis, digestion, peptide transport, glucose, sodium and water absorption, and gastrointestinal motility ( Jaworska et al, 2021 ). The RAS is important during pregnancy and acts locally in the uteroplacental unit to mediate angiogenesis, trophoblastic invasion, and adequate placentation ( Leal et al, 2022 ). It is possible that the tissue-specific functions of the RAS represent primordial functions and are the target of interventions that modulate aging.…”

Section: Introductionmentioning

confidence: 99%

Control of aging by the renin–angiotensin system: a review of C. elegans, Drosophila, and mammals

et al. 2022

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The free-living, non-parasitic nematode Caenorhabditis elegans is a premier model organism for the study of aging and longevity due to its short lifespan, powerful genetic tools, and conservation of fundamental mechanisms with mammals. Approximately 70 percent of human genes have homologs in C. elegans, including many that encode proteins in pathways that influence aging. Numerous genetic pathways have been identified in C. elegans that affect lifespan, including the dietary restriction pathway, the insulin/insulin-like growth factor (IGF) signaling pathway, and the disruption of components of the mitochondrial electron transport chain. C. elegans is also a powerful system for performing drug screens, and many lifespan-extending compounds have been reported; notably, several FDA-approved medications extend the lifespan in C. elegans, raising the possibility that they can also extend the lifespan in humans. The renin–angiotensin system (RAS) in mammals is an endocrine system that regulates blood pressure and a paracrine system that acts in a wide range of tissues to control physiological processes; it is a popular target for drugs that reduce blood pressure, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Emerging evidence indicates that this system influences aging. In C. elegans, decreasing the activity of the ACE homolog acn-1 or treatment with the ACE-inhibitor Captopril significantly extends the lifespan. In Drosophila, treatment with ACE inhibitors extends the lifespan. In rodents, manipulating the RAS with genetic or pharmacological interventions can extend the lifespan. In humans, polymorphisms in the ACE gene are associated with extreme longevity. These results suggest the RAS plays a conserved role in controlling longevity. Here, we review studies of the RAS and aging, emphasizing the potential of C. elegans as a model for understanding the mechanism of lifespan control.

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Renin-angiotensin system in normal pregnancy and in preeclampsia: A comprehensive review

Cited by 32 publications

References 61 publications

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection

The renin-angiotensin system modulates endotoxic postconditioning of exacerbated renal vasoconstriction in preeclamptic offspring

Control of aging by the renin–angiotensin system: a review of C. elegans, Drosophila, and mammals

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