Soluble Flt-1 is a circulating anti-angiogenic protein that acts by adhering to the receptor-binding domains of placental growth factor (PIGF) and VEGF, thus preventing interaction with endothelial cell surface receptors and resulting in endothelial dysfunction. During healthy pregnancy, sFlt-1 levels are low until the end of the second trimester, and PIGF levels are high, thus creating a pro-angiogenic state. As pregnancy advances, s-Flt1 levels gradually increase and the balance shifts to attenuate placental growth.
Whereas healthy maternal endothelium is crucial for the physiological adaptation to normal pregnancy, widespread endothelial dysfunction is an integral part of the multi-organ involvement of preeclampsia (Roberts and Redman, 1993). Women with pre-existing medical disorders that are characterized by endothelial dysfunction, such as hypertension and diabetes, are at increased risk of pre-eclampsia. Indeed, many of the risk factors for cardiovascular disease (all except smoking) are also risk factors for pre-eclampsia. Poor placental implantation also plays an important but not yet fully defined role toward maternal endothelial dysfunction.
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