Preclamsia

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Ther Adv Cardiovasc Dis. Author manuscript; available in PMC 2009 October 1.
Published in final edited form as: Ther Adv Cardiovasc Dis. 2008 October ; 2(5): 349–362. doi:10.1177/1753944708094529.

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Systemic and uteroplacental renin–angiotensin system in normal and pre-eclampticpregnancies
Lauren Anton and Hypertension and Vascular, Research Center, Wake, Forest University School, of Medicine, Winston-Salem, North Carolina, USA K. Bridget Brosnihan Hypertension and Vascular, Research Center, Wake, Forest University School, of Medicine, Winston-Salem, North Carolina, USA, bbrosnih@wfubmc.edu

Abstract
Pregnancy is characterized by an increase in many of the differentcomponents of the circulating renin–angiotensin system [RAS]. However, the physiological mechanisms of stimulated RAS activity during pregnancy are unknown. Even less understood is how this system may be altered in pre-eclampsia, a hypertensive disorder of pregnancy. Additional studies have shown the presence of a local tissue specific RAS in the uteroplacental unit of normal and pre-eclampticpregnancies. Differences in normal pregnant and pre-eclamptic RAS component regulation may provide insight into the mechanisms responsible for the clinical pathological features of pre-eclampsia. Specifically, this review summarizes the key findings in the circulating and uteroplacental RAS in normal and pre-eclamptic pregnancies.

Keywords pregnancy; pre-eclampsia; placenta; uterus;renin-angiotensin system; angiotensin II; angiotensin[1-7]

Hypertensive disorders of pregnancy
Despite extensive research, hypertensive disorders of pregnancy continue to be the second leading cause, behind embolism, of maternal mortality in the US accounting for almost 15% of such deaths [Working Group on High Blood Pressure in Pregnancy, 1991]. Hypertensive disorders are one of the most common medicalcomplications of pregnancy, affecting 7–10% of all pregnancies and contributing significantly to still-births and neonatal morbidity and mortality [The Working Group on High Blood Pressure in Pregnancy, 1991]. Approximately 70% of hypertensive disorders of pregnancy are due to gestational hypertension which includes pre-eclampsia and eclampsia [Moldenhauer and Sibai, 2003). Therefore, the preventionof hypertensive disorders of pregnancy, including pre-eclampsia, would have a significant impact on maternal and neonatal outcome. Unfortunately, although some of the predisposing risk factors of pre-eclampsia have been identified, there is still no proven preventative therapy. In addition, there are no predictive tests and the only known cure for pre-eclampsia is delivery, which often occursprematurely. The

Correspondence to: K. Bridget Brosnihan.

Anton and Brosnihan

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ability to prevent pre-eclampsia is limited due to the fact that its pathophysiology remains poorly understood.

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Pathophysiology of normal pregnancy and pre-eclampsia
During normal pregnancy, immediately followingimplantation, cytotrophoblast cells of embryonic origin undergo a process termed pseudovasculogenesis whereby these cells change from an epithelial to an endothelial phenotype [Zhou et al. 1997b]. This change occurs mostly through a decrease in epithelial cell specific adhesion receptors such as integrin α6β4 and Ecadherin and the onset of expression of adhesion receptors characteristic of endothelium such asVE (vascular) -cadherin, vascular cell adhesion molecule (VCAM-1), platelet-endothelial cell adhesion molecule (PECAM-1), and integrins αVβ3 and α1β1 [Zhou et al. 1997b; Vicovac et al. 1995; Damsky et al. 1992]. The functional consequence of this change in cell phenotype is to allow the cytotrophoblasts to invade the maternal uterine spiral arteries where they completely replace the endothelial...