Inflammatory mechanisms in preeclampsia

Abstract

Inflammation is a host response triggered by noxious stimuli arising during infection and/or tissue injury, and a controlled inflammatory response is beneficial to fighting infections and healing wounds. Normal pregnancy is characterised by a mild systemic inflammation, however, the inflammation may become detrimental if dysregulated, as seen in preeclampsia. Women with preeclamptic pregnancies have up to eightfold higher risk for cardiovascular diseases later in life, and genetic, clinical and molecular observations support shared underlying inflammatory mechanisms for these diseases. The discoveries that pattern recognition receptors (PRRs) directly sense inflammatory stimuli and activate innate immune cells have greatly increased our molecular understanding of inflammatory diseases. It is hypothesised that some of the clinical manifestations are caused by common underlying inflammatory mechanisms instrumented by PRRs. PRRs activate inflammatory responses by recognising endogenous damage-associated molecular patterns (DAMPs) released from injured tissues and stressed or dying cells; including degraded extracellular matrix components, heat-shock proteins, HMGB1 proteins, nucleic acids and crystalline structures such as cholesterol crystals. In preeclampsia, many such DAMPs are known to contribute to both the local placental inflammation and to systemic inflammation and endothelial dysfunction, but with largely unknown molecular action. Defining the role of PRRs in preeclampsia by learning from similar mechanisms associated with cardiovascular diseases will help us in improved understanding of this complex inflammatory syndrome.