Renal angiotensin-II receptors expression changes in a model of preeclampsia.

The blunted response to angiotensin II (Ang II) during pregnancy is lost in patients by preeclampsia. This impaired response has been attributed to a change in one or both of the Ang II receptors, type 1 (AT(1)R) and type 2 (AT(2)R). The ratio of the Ang II receptor types in the kidney has not been studied. We postulated that an imbalance exists between AT(1)R/AT(2)R receptors in the renal cortex from rats subjected to an experimental model of preeclampsia, and that this altered ratio can modify the characteristic blunted pressor response to Ang II during pregnancy. The feto-placental units of Wistar rats were made ischemic by subrenal aortic coarctation, thus creating an experimental model of preeclampsia. We measured the AT(1)R and AT(2)R protein expression and the presence of the heterodimer AT(1)R/AT(2)R in the renal cortex and evaluated the pressor response to Ang II in an isolated kidney preparation from non-pregnant, healthy pregnant, and preeclampsia model rats. Pregnancy increased AT(2)R and AT(1)R/AT(2)R heterodimer expression and decreased the pressor response to Ang II. In contrast, AT(1)R increased, while AT(2)R and AT(1)R/AT(2)R heterodimer decreased in the preeclampsia model group. Thus, Ang II hypersensitivity observed in preeclampsia might be related to an increased expression of AT(1)R over AT(2)R and to a decreased presence of the AT(1)R/AT(2)R heterodimer in renal cortex.     

The etiology of preeclampsia: the role of the father

Preeclampsia is often considered as simply a maternal disease with variable degrees of fetal involvement. More and more the unique immunogenetic maternal-paternal relationship is appreciated, and also the specific 'genetic conflict' that is characteristic of haemochorial placentation. From that perspective, pre-eclampsia can be seen as a disease of an individual couple with primarily maternal and fetal manifestations. The maternal and fetal genomes perform different roles during development. Heritable paternal, rather than maternal, imprinting of the genome is necessary for normal trophoblast development. Large population studies have estimated that 35% of the variance in susceptibility to preeclampsia is attributable to maternal genetic effects; 20% to fetal genetic effects (with similar contributions of both parents), 13% to the couple effect, less than 1% to the shared sibling environment and 32% to unmeasured factors. Not one of these large population studies focussed on the paternal contribution to preeclampsia, which is demonstrated by (1) the effect of the length of the sexual relationship; (2) the concept of primipaternity versus primigravidity; and (3) the existence of the so-called 'dangerous' father, as demonstrated in various large population studies. It is currently unknown how the father exerts this effect. Possible mechanisms include seminal cytokine levels and their effect on maternal immune deviation, specific paternal HLA characteristics and specific paternal single nucleotide polymorphisms (SNPs), in particular in the paternally expressed genes affecting placentation. Several large cohort studies, including the large international SCOPE consortium, have identified paternal SNPs with strong associations with preeclampsia.     

Vascular IL-10: a protective role in preeclampsia

IL-10 is a pregnancy compatible cytokine that plays a vital role in maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the maternal-fetal interface. Recent evidence now suggests that IL-10 is a potent vascular cytokine that can blunt hypertension and inflammation-mediated vascular dysfunction. Thus, a re-evaluation of IL-10 as a cytokine supporting endovascular interactions and angiogenesis as well as blunting hypoxic-injury and preeclampsia-like features is warranted. In this review, we highlight these novel functions of IL-10 and propose that its immune-modulating and vascular functions are mutually inclusive, particularly in the context of normal gestation.     

Mapping the theories of preeclampsia: the role of homocysteine

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia. DATA SOURCES: We searched MEDLINE, EMBASE, BIOSIS, SciSearch, and bibliographies of primary and review articles, and we contacted experts. METHODS OF STUDY SELECTION: Of the 25 relevant primary articles, 8 studies measured total serum homocysteine concentrations before the clinical onset of preeclampsia (1,876 women), whereas 17 measured it afterward (1,773 women). Meta-analytic techniques were used to examine consistency, strength, temporality, dose-response, and plausibility of the disease mechanisms implicating folate, vitamin B(6), vitamin B(12), genetic polymorphisms, oxidative stress, and endothelial dysfunction in the pathway linking hyperhomocysteinemia to preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preeclampsia than among those with uncomplicated pregnancies, but the results were heterogeneous (P = .12; I(2) = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 mumol/L versus 3.36 mumol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B(12) deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocysteinemia. CONCLUSION: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established. However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature.     

The partner's role in the etiology of preeclampsia

The etiology of preeclampsia is often considered to be purely maternal, i.e. maternal constitutional factors that impair maternal cardiovascular/endothelial mechanisms normally required to cope with the specific pregnancy demands, being primarily a generalised inflammatory response and a hyperdynamic circulation. Recent data strongly indicate an important role for the male partner in the causation of this common pregnancy disorder. The aim of this review is to discuss the relevant literature and to explain how paternal, relational and sexual factors play an important role in the etiology of preeclampsia.     

Effect of antioxidants in women with increased risk of preeclampsia. The role of oxidative stress in preeclampsia

New frontiers have been opened lately in the understanding of the patho-phisiology of preeclampsia thus giving new directions in the process of therapy of this condition. Oxidative stress is a condition characterized by peroxidants predominating over antioxidants. Numerous intensive studies are carried out to reveal the role of oxidative stress in the pathogenesis of preeclampsia.     

血浆胎盘异铁蛋白在妊娠高血压综合征发病中的作用及其预测价值

目的　探讨血浆胎盘异铁蛋白（placentalisoferritin,PLF）在妊娠高血压综合征（妊高征）发病中的作用及其对妊高征的预测价值。方法　采用前瞻性研究方法,对120例妊娠24～34周最初正常的孕妇,分别应用酶联免疫吸附试验法和Griess法,对其PLF和一氧化氮(NO)代谢产物亚硝酸基/硝酸基（NO2-/NO3-）的水平进行测定,观察孕妇孕期血压的变化并随访妊娠结局。结果　（1）120例正常孕妇中发生妊高征19例（妊高征组）,101例孕妇妊娠结局正常（正常组）。妊高征组血浆PLF水平［(285.31±53.73)mg/L］与正常组［(699.05±203.03)mg/L］比较,明显降低。两组比较,差异有极显著性（P<0.01）。妊高征组NO水平［(54.57±32.71)μmol/L］与正常组［(38.89±30.00)μmol/L］比较,明显升高(P<0.05)。血浆PLF水平与血浆NO水平呈负相关（r=0.329,P<0.01）。（2）PLF预测妊高征患者受试者工作曲线的曲线下面积为0.905。以400mg/LPLF为切点预测妊高征时的敏感性、特异性、阳性预测值及阴性预测值,分别为100.00％、85.15％、55.88％、100.00％,Kappa指数为0.645。结论　妊高征患者血浆PLF水平降低,PLF与妊高征的发生有密切关系。血浆PLF水平可作为妊高征的预测指标之一。     

血脂干预对子痫前期早期预防作用

为了维持妊娠的正常进行、胎儿生长发育、产后哺乳等特殊需求,孕期必须有一定量的脂肪储备。正常妊娠期间血脂高于正常,但研究表明,子痫前期患者较正常孕妇血脂水平明显增高。血脂异常可能通过氧化应激、炎性反应等损伤血管内皮细胞功能,引起子痫前期的发展。孕前早期通过饮食控制、运动干预及必要的药物治疗控制血脂在正常范围,并且孕期合理饮食、适当运动对预防子痫前期的发生具有重要作用,但孕期药物降脂是否合理仍需大量证据进一步证实。     

The renin-angiotensin-aldosterone system in preeclampsia. A review.

The renin-angiotensin-aldosterone system plays an integral role in the (patho)physiology of pregnancy and pregnancy-induced hypertensive disease. The current review concerns the renin-angiotensin-aldosterone system in relation to other vasoactive substances in normal pregnancy and preeclampsia.