Molecular mechanisms of maternal vascular dysfunction in preeclampsia

•Endothelium-derived factor production and signaling are altered in preeclampsia. •Placenta-derived factors induce systemic maternal vascular dysfunction. In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. molecules produced in the vascular endothelium that signal smooth muscle cells in blood vessel walls to contract, constricting the blood vessel. EDCFs are released in response to various stimuli, such as Ang II, arachidonic acid, hypoxia, stretch, and the superoxide anion. Release of EDCFs is associated with pathological conditions. molecules produced in the vascular endothelium that signal smooth muscle cells in blood vessel walls to relax, dilating the blood vessel. a chronic medical condition in which the blood pressure in the arteries is elevated. attenuated growth of a fetus; the fetus does not reach its growth potential while in the mother's womb. In cases of IUGR, the growing fetus weighs less than 90% of other babies at the same gestational age. a lectin-like 52-kD receptor that mediates the recognition, internalization, and degradation of oxLDL by vascular endothelial cells. vesicles >100 nm in diameter that are released into the circulation via shedding from activated or apoptotic cells. contains 37 genes and approximately 16 600 bp; organized as a circular, covalently closed, double-stranded DNA in most multicellular organisms. free radical with cell signaling properties. a physiological state that describes an imbalance between the production of free radicals and antioxidant defense mechanisms. relating to or occurring in the period of time following the birth of a child. a lipid molecule and member of the eicosanoid family that is released by healthy endothelium and induces smooth muscle relaxation. the presence of an excess of serum proteins in the urine. chemically reactive molecules containing oxygen that play a role in cell signaling and homeostasis. small blood vessels that constitute the main part of total vascular resistance to blood flow. corkscrew-like arteries of the endometrium that are sensitive to hormonal and growth factor influences in the non-pregnant endometrium. Undergo remodeling and vascular smooth muscle disorganization during pregnancy due to the phenomenon of trophoblast invasion. single, membrane-spanning, noncatalytic receptors that recognize structurally conserved molecules derived from microbes (pathogen-associated molecular patterns) or dying cells (damage-associated molecular patterns). specialized cells of the placenta.