Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

Abstract

Preeclampsia is a complex hypertensive disorder in pregnancy which can be lethal and is responsible for more than 70,000 maternal deaths worldwide every year. Besides the higher risk of unfavorable obstetric outcomes in women with preeclampsia, another crucial aspect that needs to be considered is the association between preeclampsia and the postpartum cardiovascular health of the mother. Currently, preeclampsia is classified as one of the major risk factors of cardiovascular disease (CVD) in women, which doubles the risk of venous thromboembolic events, stroke, and ischemic heart disease. In order to comprehend the pathophysiology behind the linkage between preeclampsia and the development of postpartum CVD, a thorough understanding of the abnormal uteroplacental vascular remodeling in preeclampsia is essential. Therefore, this review aims to summarize the current knowledge of the defective process of spiral artery remodeling in preeclampsia and how the resulting placental damage leads to excessive angiogenic imbalance and systemic inflammation in long term CVD. Key molecular factors in the pathway—including novel findings of microRNAs—will be discussed with suggestions of future management strategies of preventing CVD in women with a history of preeclampsia.

Expression of Vascular Endothelial Growth Factor in the Placenta of Iraqi Women Complicated with Hypertensive Disorder

“…18 Additionally, dis-regulation was proposed in the VEGF family and two possible mechanisms for interpreting defective vascular formation: one was the down-regulation of membranerestricted VEGF-1 receptors (VEGFR-1) in the placenta leading to the development of the defective uteroplacental development, and the second was the over-production of inexpensive soluble VEGF-1, which could suppress the effects of VEGF and PIGF. 19,20 The hypoxia environment that stimulates VEGF production may have different advantages in terms of severity and enhanced factors in cases of high blood pressure. However, despite high levels, the dis-regulation occurred at the receptor level leading to a defect in VEGF-A and the generation of defective vessels.…”

Flow-Responsive Noncoding RNAs in the Vascular System: Basic Mechanisms for the Clinician

“…LncRNA are able to exert an array of biological func tions, including: (1) regulation of DNA transcription by acting with a transcription facto (2) epigenetic silencing and repressing the histone modification via chromatin interaction (3) mRNA translation (4) post-translational regulation through miRNA sponges o circRNA, (5) scaffold of protein complex, (6) shorter ncRNAs (siRNA) generation (Figur 1B). Noncoding RNAs are largely involved in cardiovascular physiology, atherosclerosi [35], and multiple cardiovascular diseases [36], as chronic and acute coronary syndrome [6,[37][38][39][40][41], vascular remodeling [29,42], valvular heart disease [43][44][45][46][47], generation and pro gression of ectopic calcifications in the cardiovascular system [48][49][50][51][52][53][54], platelet functio [55][56][57][58][59], heart failure and stroke [60][61][62][63][64][65][66][67][68][69][70]. Evidence of the impact of flow conditions on cir culating ncRNA derives both from observations on pathological changes, such as cardia valve disease, vascular stenoses or aneurysm, but also from physiological conditions, suc as exercise [68].…”

“…This review focuses on regulatory noncoding RNAs that are directly or indirectl responsive to flow and their involvement with cardiovascular effects of altered bloo flow, with a focus on the potential clinical relevance and the underlying molecular mech anisms and their possible use as clinical biomarkers [71]. As relevant evidence is no equally available for all ncRNAs sub-categories, some specific ncRNAs, including siR NAs, snoRNA or piRNA are not mentioned in this review due to lack of evidence in rela Noncoding RNAs are largely involved in cardiovascular physiology, atherosclerosis [35], and multiple cardiovascular diseases [36], as chronic and acute coronary syndromes [6,[37][38][39][40][41], vascular remodeling [29,42], valvular heart disease [43][44][45][46][47], generation and progression of ectopic calcifications in the cardiovascular system [48][49][50][51][52][53][54], platelet function [55][56][57][58][59], heart failure and stroke [60][61][62][63][64][65][66][67][68][69][70]. Evidence of the impact of flow conditions on circulating ncRNA derives both from observations on pathological changes, such as cardiac valve disease, vascular stenoses or aneurysm, but also from physiological conditions, such as exercise…”

The role of biomarkers in early prediction and molecular mechanisms of preeclampsia

“…Consequently, deep placentation is unsuccessful and the placenta՚s blood flow is constrained, resulting in insufficient perfusion by the uterus. This phenomenon is associated with PE as well as many other pregnancy complications, such as placental abruption, preterm labor, premature rupture of membranes and intrauterine fetal mortality [20].…”