About 5 percent of pregnancies suffer complications from abnormal placental development. The process of placentation begins when blastocysts adhere to the uterine endometrium, forming a lineage of epithelial cells termed the invasive extravillous cytotrophoblast, which then invades the uterine wall to create the decidua, transforming the spiral arteries into a low-resistance uteroplacental circulation.
Impaired development of the uteroplacental vasculature, therefore, has its origins in the first trimester as a result of an abnormal interaction between the invading extravillous cytotrophoblast and the maternal immune system, resulting in decidual vasculopathy, with small, poorly developed spiral arteries. As these pregnancies progress, placental ischemia and infarction may result in a maternal placental syndrome—pre-eclampsia, placental abruption, and/or the ensuing adverse perinatal outcomes, including fetal growth restriction and stillbirth.
It was previously thought that the consequences of maternal placental disease resolved quickly and completely after delivery of the placenta. More recently, however, it has become clear that placental disease, as a major basis of the maternal placental syndrome, is a marker of future vascular disease, forecasting a vastly different health trajectory than that of a woman who has had normal placental function and a healthy pregnancy.
Irgens HU, et al.. Long term mortality of mothers and fathers after pre-eclampsia: Population based cohort study. BMJ 2001; 323:1213–1217.
Ray JG, et al.. Cardiovascular health after maternal placental syndromes (CHAMPS): Population-based retrospective cohort study. Lancet 2005; 366:1797–1803.
Vikse BE, et al.. Previous preeclampsia and risk for progression of biopsy-verified kidney disease to end-stage renal disease. Nephrol Dial Transplant 2010; 25:3289–3296.
Mongraw-Chaffin ML, et al.. Preeclampsia and cardiovascular disease death: Prospective evidence from the child health and development studies cohort. Hypertension 2010; 56:166–171.
Kanasaki K, et al.. Deficiency in catechol-o-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature 2008; 453:1117–1121.
Bourghardt J, et al.. The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice. Endocrinology 2007; 148:4128–4132.
Roten LT, et al.. A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2). Mol Hum Reprod 2011, in press.
Voutilainen S, et al.. Functional COMT Val158met polymorphism, risk of acute coronary events and serum homocysteine: The Kuopio ischaemic heart disease risk factor study. PLoS One 2007; 2:e181.
Morgan T, et al.. Angiotensinogen t235 expression is elevated in decidual spiral arteries. J Clin Invest 1997; 100:1406–1415.
Johansson A, et al.. Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease. Eur J Hum Genet 2011, in press.
Savvidou MD, et al.. Endothelial nitric oxide synthase gene polymorphism and maternal vascular adaptation to pregnancy. Hypertension 2001; 38:1289–1293.
Oney T, Kaulhausen H. The value of the angiotensin sensitivity test in the early diagnosis of hypertensive disorders in pregnancy. Am J Obstet Gynecol 1982; 142:17–20.
Wallukat G, et al.. Agonistic autoantibodies directed against the angiotensin II AT1 receptor in patients with preeclampsia. Can J Physiol Pharmacol 2003; 81:79–83.
Herse F, et al.. Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia. Hypertension 2007; 49:604–611.
Saxena AR, et al.. Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension 2010; 55:1239–1245.
Brodszki J, et al.. Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch. Acta Obstet Gynecol Scand 2008; 87:154–162.
Yinon Y, et al.. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: Insights into future vascular risk. Circulation 2010; 122:1846–1853.
Sugawara J, et al.. Decrease and senescence of endothelial progenitor cells in patients with preeclampsia. J Clin Endocrinol Metab 2005; 90:5329–5332.
Luppi P, et al.. Maternal circulating cd34+vegfr-2+ and cd133+vegfr-2 + progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia. Reprod Sci 2010; 17:643–652.
Romundstad PR, et al.. Hypertension in pregnancy and later cardiovascular risk: Common antecedents? Circulation 2010; 122:579–584.