The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

Abstract

Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. It afflicts 2–8% of pregnancies and is the most common cause of gestational hypertension. This article is focused on nuclear factor kappa B (NF-κB), its role in normal and pathological spiral arteries remodelling and development of preeclampsia, with evaluation if it is a promising therapeutic target. NF-κB is a key mediator of placentation. Since insemination, it stimulates production of proinflammatory cytokines by the uterine epithelium, which leads to activation of macrophages, uterine natural killer cells (uNKs), and other leukocytes. The trophoblast/uNK/macrophage crosstalk is crucial for implantation and spiral arteries remodeling, and NF-κB regulates that process through modification of cytokine expression, as well as cell phenotype and function. In the course of preeclampsia, the remodeling processes is disturbed by excessive inflammation and increased NF-κB activation. The pathological remodeling leads to uteroplacental dysfunction, release of proinflammatory cytokines into the maternal circulation, endothelial stress, and development of preeclampsia. The analysis of genetic and environmental inductors of NF-κB helps to distinguish preeclampsia risk groups. Furthermore, a selective inhibition of NF-κB or NF-κB activating pathways alleviates symptoms of preeclampsia in rat models; therefore, this could be an efficient therapeutic option.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes

“…This process is exacerbated in PE, but occurs naturally during gestation. Furthermore, in PE, there is an overactivation of NF-κB, contributing to induce the expression of proinflammatory and antiangiogenic proteins, further elevating oxidative stress, inflammation, and vascular dysfunction [9,45,46]. Besides, during the trophoblastic invasion, the decidua contains a lot of necessary immune system cells to promote this process, such as macrophages, natural killer (NK) cells, T cells, and regulatory T cells (Treg).…”

“…This process is exacerbated in PE, but occurs naturally during gestation. Furthermore, in PE, there is an overactivation of NF- κ B, contributing to induce the expression of proinflammatory and antiangiogenic proteins, further elevating oxidative stress, inflammation, and vascular dysfunction [ 9 , 45 , 46 ].…”

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

“…They then were able to explore the most relevant miRNA in endometriosis [148][149][150]. This information is critical since directed therapies depending on endometriosis may provide new elements to control the inflammatory disease and aid in fertilization [148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163][164][165][166]. In addition, exosomes contain miRNA and other proteins.…”

“…Modulation of PD1/PDL1 is also essential in understanding NK responses in the endometrium and the possible role of this diad in preeclampsia [156][157][158][159][160]. This diad's mechanism may depend upon the inflammatory burden and the expression of markers of downregulation on NK cells.…”

“…This diad's mechanism may depend upon the inflammatory burden and the expression of markers of downregulation on NK cells. The inflammatory response generated by pathogens of tumour cells in the endometrium involves NfkB, which also seems vital in uterine artery remodeling [160].…”