Role of ROS/RNS in Preeclampsia: Are Connexins the Missing Piece?

Abstract

<jats:p>Preeclampsia is a pregnancy complication that appears after 20 weeks of gestation and is characterized by hypertension and proteinuria, affecting both mother and offspring. The cellular and molecular mechanisms that cause the development of preeclampsia are poorly understood. An important feature of preeclampsia is an increase in oxygen and nitrogen derived free radicals (reactive oxygen species/reactive nitrogen species (ROS/RNS), which seem to be central players setting the development and progression of preeclampsia. Cell-to-cell communication may be disrupted as well. Connexins (Cxs), a family of transmembrane proteins that form hemichannels and gap junction channels (GJCs), are essential in paracrine and autocrine cell communication, allowing the movement of signaling molecules between cells as well as between the cytoplasm and the extracellular media. GJCs and hemichannels are fundamental for communication between endothelial and smooth muscle cells and, therefore, in the control of vascular contraction and relaxation. In systemic vasculature, the activity of GJCs and hemichannels is modulated by ROS and RNS. Cxs participate in the development of the placenta and are expressed in placental vasculature. However, it is unknown whether Cxs are modulated by ROS/RNS in the placenta, or whether this potential modulation contributes to the pathogenesis of preeclampsia. Our review addresses the possible role of Cxs in preeclampsia, and the plausible modulation of Cxs-formed channels by ROS and RNS. We suggest these factors may contribute to the development of preeclampsia.</jats:p>

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

“…Oxidative stress is observed in PE, where the levels of ROS are elevated, resulting in impaired NO signaling and vascular dysfunction. In PE, excess levels of all ROS are reported to be more prevalent, including superoxide superoxide (O 2 ·), hydrogen peroxide (H 2 O 2 ), hydroxyl radical (OH) and peroxynitrite (ONOO−) ( Agarwal et al, 2005 ; Rozas-Villanueva et al, 2020 ). In our work presented, we successfully constructed an oxidative stress model in vitro in cultured TEV-1 cells by H 2 O 2 treatment (500 μM, 3 h) that significantly induced ROS levels to 1.8 folds, which is consistent with previous reports ( Haendeler et al, 2005 ; Gao et al, 2020 ).…”

Pre-Pregnancy Obesity vs. Other Risk Factors in Probability Models of Preeclampsia and Gestational Hypertension

“…The etiology of pregnancy-induced hypertension is not fully explained, but the pathogenesis of PE takes into account disturbances in trophoblast invasion into the walls of the spiral arteries, which results in a lack of remodeling, high-resistance circulation, and placental ischemia [37,38]. The balance of many placental biomarkers is disturbed, oxidative stress and inflammation in both the placenta and in the mother's circulation are intensified, and the effect is endothelial function damage and an increase in blood pressure [16,[37][38][39]. There are many studies available in the literature which have found associations between lower levels of antioxidants in pregnant women with PE [40].…”

Gap Junctions and Hemichannels Composed of Connexins and Pannexins Mediate the Secondary Brain Injury Following Intracerebral Hemorrhage

“…Following ICH progression, the accumulation of ROS induces oxidative stress, which contributes to SBI caused by inflammation and BBB disruption [ 4 ]. Interestingly, ROS/RNS are involved in regulating the change of connexin and pannexin-based channel properties, both in systemic vasculature and brain cells [ 58 , 59 ]. Moreover, oxidation products were shown to increase hemichannel activity whilst reducing GJIC [ 60 ].…”