Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review

Naidoo, Nitalia; Moodley, Jagidesa; Khaliq, Olive P.; Naicker, Thajasvarie

doi:10.1016/j.virusres.2022.198880

Cited by 9 publications

(9 citation statements)

References 187 publications

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“…Katopodis et al noticed 69 miRNAs having a strong binding potential against NRP1 [ 42 ]. Furthermore, Naidoo et al stated that several miRNAs might downregulate NRP1 (miR-320(a-d), miR-124-3p, miR-214-3p, miR-206, miR-199a-5p, miR-24-3p, miR-130a-3p, and miR-141-3p), while it was pointed that miR-204 was overexpressed in COVID-19 disease [ 43 ]. Moreover, Mone et al demonstrated that miR-24 targets 3`UTR of NRP1 [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

et al. 2023

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During the last three years, since the emergence of the COVID-19 pandemic, a significant number of scientific publications have focused on resolving susceptibility to the infection, as well as the course of the disease and potential long-term complications. COVID-19 is widely considered as a multisystem disease and a variety of socioeconomic, medical, and genetic/epigenetic factors may contribute to the disease severity and outcome. Furthermore, the SARS-COV-2 infection may trigger pathological processes and accelerate underlying conditions to clinical entities. The development of specific and sensitive biomarkers that are easy to obtain will allow for patient stratification, prevention, prognosis, and more individualized treatments for COVID-19. miRNAs are proposed as promising biomarkers for different aspects of COVID-19 disease (susceptibility, severity, complication course, outcome, and therapeutic possibilities). This review summarizes the most relevant findings concerning miRNA involvement in COVID-19 pathology. Additionally, the role of miRNAs in wide range of complications due to accompanied and/or underlying health conditions is discussed. The importance of understanding the functional relationships between different conditions, such as pregnancy, obesity, or neurological diseases, with COVID-19 is also highlighted.

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Section: Resultsmentioning

confidence: 99%

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

et al. 2023

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“…The resultant effect is an increase in the release of pro-inflammatory cytokines including interleukins (IL-1β, IL-6, IL-2, IL-8), interferon-gamma (INF-γ), tumour necrosis factor-alpha (TNF-α), and syncytiotrophoblast microparticles (STBM) which further prevents the synthesis of eNOS and therefore reduced vasodilation which is maintained by placental oxidative stress [ 55 , 56 ]. Ultimately, the anti-angiogenic and pro-inflammatory state of PE favors vasoconstriction primarily due to heightened systemic expression of the powerful vasoconstrictor, endothelin-1 (ET-1) which is maintained by calcium influx and vascular resistance during endothelial damage in PE [ 16 , 57 ]. Moreover, Lely et al characterized PE as expressing decreased VEGFR-2 and sVEGFR-2 in maternal circulation [ 58 ].…”

Section: Vascular Endothelial Growth Factor Receptor 2 In Preeclampsiamentioning

confidence: 99%

“…Furthermore, VEGFR-2 is significantly downregulated in LOPE compared to EOPE [ 62 ]. This may be due to widespread maternal vascular endothelial damage evident in LOPE [ 10 , 57 ]. Importantly, these investigations did not report whether the placental samples were obtained before labour since labour is associated with an increased release of placental proteins, including VEGF [ 63 ].…”

Section: Vascular Endothelial Growth Factor Receptor 2 In Preeclampsiamentioning

confidence: 99%

“…The sFlt-1/PlGF ratio is a powerful diagnostic tool that is currently used in the early diagnosis and management of PE worldwide [ 109 ]. Thus, it is plausible that SARS-CoV-2 infection may heighten the risk of developing PE while PE may increase the risk of developing severe COVID-19 [ 57 , 110 ].…”

Section: Sars-cov-2 Infection and The Influence Of Vegf And Its Recep...mentioning

confidence: 99%

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Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Abel

Moodley

Khaliq

et al. 2022

IJMS

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This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

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“…Neuropilin-1 (NRP-1) is a versatile transmembrane protein involved in cell migration and invasion, angiogenesis, tumorigenesis, axonal guidance, immune response regulation, and entry of several viruses (i.e., severe acute respiratory syndrome coronavirus 2, human T-cell lymphotropic virus type 1, and Epstein–Barr virus) into the host cell (Naidoo et al. 2022 ). It serves as a co-receptor for the binding of angiogenic ligands such as vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), human growth factor (HGF), and platelet-derived growth factor (PDGF) (Elpek 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Immunoexpression of neuropilin-1 in the chorionic villi of HIV-infected preeclamptic South African women of African ancestry

Naidoo

Abel

Moodley

et al. 2023

Histochem Cell Biol

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Neuropilin-1 (NRP-1) is an essential regulator of maternal immune tolerance, placentation, and angiogenesis. Its dysregulation in preeclampsia (PE) and human immunodeficiency virus (HIV) infection implicates NRP-1 in disease susceptibility and progression. Therefore, this study investigates placental NRP-1 immunoexpression in HIV-complicated preeclamptic pregnancies in South African women of African ancestry receiving antiretroviral therapy. Immunohistochemistry of recombinant anti-neuropilin-1 antibody was performed on placental tissue from 30 normotensive and 60 early onset (EOPE) and late-onset (LOPE) preeclamptic women stratified by HIV status. Qualitative analysis of NRP-1 immunostaining within the chorionic villi revealed a predominant localization in trophoblasts and syncytial knots as well as endothelial, fibroblast-like, and Hofbauer cells. Following morphometric evaluation, we report that PE and HIV infection and/or antiretroviral usage independently downregulate placental NRP-1 immunoexpression; however, as a comorbidity, this decline is further augmented within the conducting and exchange villi. Furthermore, reduced immunoexpression of NRP-1 in EOPE compared with LOPE villi may be due to maternal–fetal maladaptation. It is plausible that the decreased NRP-1 immunoexpression in PE placentae facilitates syncytiotrophoblast apoptosis and subsequent deportation of NRP-1 into the maternal circulation, contributing to the anti-angiogenic milieu of PE. We hypothesize that the intense NRP-1 immunoreactivity observed in Hofbauer cells at the maternal–fetal interface may contribute to the natural prevention mechanism of HIV vertical transmission.

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Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review

Cited by 9 publications

References 187 publications

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Immunoexpression of neuropilin-1 in the chorionic villi of HIV-infected preeclamptic South African women of African ancestry

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