MicroRNAs targeting VEGF are related to vascular dysfunction in preeclampsia

Abstract

In preeclampsia (PE) pre-existent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. The vascular endothelial growth factor (VEGF) pathway is essential in the placentation process and VEGF expression is regulated through post-transcriptional modification by microRNAs. We investigated the expression of VEGF related circulating miR-16, miR-29b, miR-126, miR-155 and miR-200c in PE versus healthy pregnancies (HP), and their relation with vascular function, oxidative stress and systemic inflammation.In this case-control study, 24 women with early PE (in vivo vascular function (flow mediated dilation (FMD), modified FMD (mFMD), carotid-femoral pulse wave velocity (CF-PWV), augmentation index (AIx75) and reactive hyperaemia index (RHI)). FMD, CF-PWV, AIx75 and RHI were all significantly impaired in PE (p<0.05). PE patients had reduced levels of miR-16 (5.53±0.36vs5.84±0.61) and increased levels of miR-200c (1.34±0.57vs0.97±0.68) (p<0.05). Independent of age and parity, miR-16 was related to impaired FMD (ß 2.771, 95% C.I. 0.023-5.519, p=0.048) and mFMD (ß3.401, 95% C.I. 0.201-6.602, p=0.038). Likewise, miR-200c was independently associated with CF-PWV (ß0.513, 95% C.I. 0.034-0.992, p=0.036). In conclusion, circulating levels of miR-16 were lower in PE, which correlated with impaired endothelial function. Circulating miR-200c was increased in PE and correlated with higher arterial stiffness. These findings suggest a post-transcriptional dysregulation of the VEGF pathway in PE and identify miR-16 and miR-200c as possible diagnostic biomarkers for PE.

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis

“…Its increased expression level was associated with a decreased level of pro-angiogenic factor, VEGF, in an experimental rat model of PE (Cheng et al, 2011). Newly performed studies have reported significantly higher levels of miRNA-155 in the maternal peripheral blood of women with compared to women without PE (Ayoub et al, 2019;Youssef and Marei, 2019;Witvrouwen et al, 2021).…”

Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia

“…Moreover, VEGF expression is also regulated by post-transcriptional modification of micro-RNAs (miRNAs). In particular, for miR-16, significant changes in miR-200c were observed [ 49 ]. This shows that the above expressed molecules are related to one another.…”

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

“…[ Table 2 ] demonstrates that four miRNAs (miR-200c, miR-141, miR-214, and miR-29b) are common to pro-inflammatory conditions such as PE and COVID-19, implicating their role in evoking the immune response, similarly to their role in other inflammatory diseases ( Reddy et al, 2012 ; Chen et al, 2020 ; Guo et al, 2021 ). Notably, these four miRNAs have been previously described as anti-angiogenic miRNAs ( Zhao et al, 2017 ; Dong et al, 2019 ; Tang et al, 2020 ; Witvrouwen et al, 2021 ). Furthermore, anti-angiogenic miRNAs, miR-206, miR-320, miR-365, miR-181b, and miR-24 were overexpressed in PE; however, miR-181b and miR-24 were anti-inflammatory in previous studies ( Wu et al, 2014 ; Fu et al, 2016 ; Liang et al, 2016 ; Xu et al, 2020 ; Green et al, 2021 ; Liu and Li, 2021 ; Wu et al, 2021 ; Yuan et al, 2021 ).…”

“…Pro-inflammatory miRNAs (miR-320, miR-199a-5p, miR-200c, miR-29b) were repressed, while anti-inflammatory miR-24 was overexpressed in HIV-1 infection due to reduced immunocompetence ( Reddy et al, 2012 ; Lorenzen et al, 2014 ; Zhang et al, 2015 ; Chen et al, 2020 ; Liu and Li, 2021 ). Interestingly, these miRNAs are all anti-angiogenic, implicating the role of HIV-1 infection, particularly the involvement of tat, in angiogenic dysregulation ( Chan et al, 2012 ; Wu et al, 2014 ; Tang et al, 2020 ; Xu et al, 2020 ; Witvrouwen et al, 2021 ). Although HIV-1 infection results in an immunocompromised state, overexpression of inflammatory miRNAs (miR-206, miR-365, and 214) and repression of miR-181b and miR-141 (anti-inflammatory miRNAs) may occur due to the immune reconstitution effect of ART and/or inconsistent data ( Sun et al, 2012 ; Fu et al, 2016 ; Tooke et al, 2016 ; Wang et al, 2018 ; Guo et al, 2021 ; Li, Li, Chen, et al, 2021 ; Wu et al, 2021 ).…”