Preeclampsia: Vascular Pathophysiological Mechanism and the Basis for Early Diagnosis and Treatment

Abstract

Rev Bras Ginecol Obstet 2016;38:369-372. Hypertensive disease of pregnancy, postpartum hemorrhage and infectious syndromes in pregnancy and puerperium are the leading causes of morbidity and mortality for pregnant women around the world. 1 Their frequency varies according to the country and accessibility to health care. 1 Hypertensive diseases, including preeclampsia, complicate 2-10% of all pregnancies. 1-3 In Latin America and the Caribbean, hypertensive disorders are responsible for at least 26% of maternal deaths. 3 Preeclampsia is a multifactorial disease caused by environmental factors that act over a genetic base, permitting the occurrence of this disorder. 4-12 Based on this premise, the risk factors considered for the development of this disease are: overweightness; obesity; nulliparity and multiparity; being at the extremes of reproductive life; vascular diseases, such as chronic hypertension; metabolic diseases, such as diabetes mellitus; collagen diseases, such as systemic lupus erythematosus; multiple pregnancies; maternal and paternal family history 12-14 (paternal imprinting expressed in the mother); pregnancy by assisted reproductive techniques; 12 micropolycystic ovary syndrome with insulin resistance; 15 severe anemia; 16 antiphospholipid syndrome; 17 and low-calcium diets consumed by people living at high altitudes. 18,19 The interaction of risk factors and multiple polymorphic genes induces the synthesis of several proteins with effects differing from their original function, leading to the impairment of placental perfusion and the consequent production of mediators that damage the endothelium. The main proteins and others factors involved are listed below. 7,8,20 Group I -vasoactive and vascular remodeling proteins: nitric oxide synthase; renin; type I and II angiotensin receptors; angiotensin converting enzyme; polycarboxypeptidase; endothelin-1; alpha and beta estrogen receptors; endoglin; tyrosine-kinase fms-like receptor-1; placental growth factor; and vascular endothelial growth factor. 20Group II -thrombophilia and hypofibrinolysis: methyltetrahydrofolate reductase; Leiden Factor V; prothrombin; fetal thrombophilia; plasminogen activator inhibitor-1; B3 integrin; and glycoprotein IIIA. 20Group III -oxidative stress, lipid metabolism, endothelial injury: epoxide hydrolase; glutathione transferase; superoxide dismutase; cytochrome P450 1A1; lipoprotein lipase; apolipoprotein E; and long-chain 3-hydroxyacylCoA dehydrogenase. 20Group IV -immunogenetic: human leukocyte antigen; interleukins 1 and 10; and tumor necrosis factor. 20 Physiologically, in order to promote vascular remodeling, the changes of the decidua also occur in the inner area of the myometrium. 21 An interaction of trophoblastic human leukocyte antigen (HLA) C, HLA-E, HLA-G with natural killer cells or dendritic cells or both is necessary for this event to occur. The presence of certain combinations of HLA-C and isoform types of immunoglobulin receptors bound to natural killer cells predispose to preeclampsia. [22][23][24]...

Uterine Artery Doppler Ultrasonography for First Trimester Prediction of Preeclampsia in Individuals at Risk from Low-Resource Settings

“…Despite an adaptive response in the early phase, systemic circulation alterations and an imbalance of vasoactive factors occur. Trophoblast invasion failure, supposedly due to the interaction between exposure to risk, presence of polymorphic genes and several other factors (vasoactive and vascular remodeling proteins, thrombophilia, hypofibrinolysis, oxidative stress, lipid metabolism, endothelial injury and immunogenetic factors), deters physiological remodeling in the spiral arteriolar walls [9]. Changes in these physiological processes determine high resistance circulation in the terminal vascular territory of spiral arteries.…”

Síndromes hipertensivas gestacionais: impacto da pré-eclâmpsia na saúde das gestantes

“…A etiologia da pré-eclâmpsia ainda não foi totalmente elucidada e definida cientificamente. Porém as gestações desencadeiam uma série de alterações no organismo da gestante, podendo gerar um aumento exacerbado da massa placentária, o que parece auxiliar no desenvolvimento da pré-eclâmpsia (Oliveira et al, 2016), no entanto, é improvável que exista apenas uma causa, há necessidade de maiores esclarecimentos etiológicos (Chávez, 2016). Apesar deste empecilho, associado à etiologia desconhecida da pré-eclâmpsia, alguns fatores predisponentes já identificados, são utilizados como norteadores, auxiliando na conduta do pré-natal (Peraçoli et al, 2019), esse avanço contribuiu significativamente para uma melhor prevenção da pré-eclâmpsia e consequentemente diminuição nas taxas morbidade e mortalidade materna e perinatal (Chávez, 2016).…”

CTHRC1 promotes growth, migration and invasion of trophoblasts via reciprocal Wnt/β-catenin regulation

“…PE is one of the most feared pregnancy complications, occurring in 3-5 % of pregnancies in developed countries, and up to 10 % in developing countries (Taylor 1997;Say et al 2014). The pathophysiology of PE has not been fully elucidated; however, it is well known that PE is associated with impaired trophoblast invasion in early pregnancy, which can cause subsequently angiogenic imbalance and oxidative stress, and finally result in endothelial cell dysfunction during later gestation periods (Chau et al 2017;Chávez and Cavalli 2016;Maynard and Karumanchi 2011;Roberts and Speer 2004). Therefore, an investigation of the molecular mechanisms involved in the regulation of migration and invasion of trophoblast cells is important for understanding the pathogenesis of PE.…”