The Role of Inflammation in the Pathogenesis of Preeclampsia

Abstract

Preeclampsia (PE) affects 5-8% of pregnant women, and it is the major cause of perinatal morbidity and mortality. It is defined as arterial hypertension in women after 20 weeks of gestation which cooccurs with proteinuria (300 mg/d) or as arterial hypertension which is accompanied by one of the following: renal failure, liver dysfunction, hematological or neurological abnormalities, intrauterine growth restriction, or uteroplacental insufficiency. Currently, pathophysiology of preeclampsia poses a considerable challenge for perinatology. Preeclampsia is characterized by excessive and progressive activation of the immune system along with an increase in proinflammatory cytokines and antiangiogenic factors in fetoplacental unit as well as in vascular endothelium in pregnant women. A single, major underlying mechanism of preeclampsia is yet to be identified. This paper discusses the current understanding of the mechanisms which underlie the development of the condition. Some significant factors responsible for PE development include oxidative stress, abnormal concentration and activity in mononuclear phagocytic system, altered levels of angiogenic and antiangiogenic factors, and impaired inflammatory response triggered by inflammasomes. Detailed understanding of pathophysiology of inflammatory process in PE can largely contribute to new, targeted anti-inflammatory therapies that may improve perinatal outcomes in PE patients.

Predicting factors of adverse pregnancy outcomes in Thai patients with systemic lupus erythematosus

“…The pathogenic mechanisms of PIH and pre-eclampsia are not clear, but have been reviewed widely, and included innate immunity, [ 33 ] bioactive factors (such as inflammatory cytokines, angiogenetic factors, growth factors, etc. ), [ 34 , 35 ] oxidative stress, [ 36 ] placental vascular maladaptation, [ 37 ] and endothelial dysfunction. [ 38 , 39 ] Among these, endothelial dysfunction is the most likely underlying mechanism, [ 39 ] which causes imbalance between an endothelial-derived vasodilator (such as nitric oxide and prostacyclin) and vasoconstrictors (such as endothelin-1, thromboxane A2), leading to the promotion of vasoconstriction, hypertension, and pre-eclampsia.…”

Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia

“…The reduced bioavailability of NO and oxidative stress are thought to play a key role in the maternal-placental circulation and in poor placentation ( Fig. 1 ) [ 10 , [31] , [32] , [33] , [34] , [35] ].…”

“…The presence of endothelial cell activation markers is a characteristic of PE pathogenesis, characterized by increased levels of von Willebrand factor, endothelin, thrombomodulin and fibronectin in the maternal systemic circulation [ [1] , [2] , [3] , [4] , [5] , [6] , [32] , [33] , [34] , [35] , [36] , [37] ]. The identification of sFlt-1 and endoglin, produced in excessive amounts during PE, revealed the links between placental abnormality and endothelial dysfunction [ 38 , 39 ].…”

“…A large body of evidence indicates that oxidative stress plays a key-role throughout the pathophysiology of PE, more in early onset than in late onset PE, because the poor uteroplacental perfusion resulting from the defective spiral artery remodeling, generates a large amount of ROS [ 32 ]. This places oxidative stress as a major cause of cytokines and anti-angiogenic factors release in the maternal circulation, subsequently leading to endothelial dysfunction and inflammation, together with the decrease in NO bioavailability and the dysfunctional eNOS activity in placenta [ [32] , [33] , [34] , [35] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] ]. The causes of these events are not fully identified.…”

“…There is also a decrease in superoxide dismutase (SOD) activity and plasma thiol levels, while ceruloplasmin levels increase, suggesting a certain level of “physiological stress” during normal pregnancy through the production of ROS [ 33 , 35 , 64 ]. Moderate ROS levels are implicated in proliferation and cell maturation required for pregnancy maintenance and embryo development [ 65 , 66 ].…”