Velloso E P, Vieira R, Cabral A C, Kalapothakis E, Santos R A S
Departamento de Fsiologia [corrected] Universidade Federal de Minas Gerais, Belo Horizonte, MG [corrected] Brasil.
Braz J Med Biol Res. 2007 Apr;40(4):583-90. doi: 10.1590/s0100-879x2007000400018.
The relationship between preeclampsia and the renin-angiotensin system (RAS) is poorly understood. Angiotensin I-converting enzyme (ACE) is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II) and inactivating the vasodilator angiotensin-(1-7) (Ang-(1-7)). ACE (I/D) polymorphism is characterized by the insertion (I) or deletion (D) of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D) polymorphism was correlated with plasma Ang-(1-7) levels and several RAS components in both preeclamptic (N = 20) and normotensive pregnant women (N = 20). The percentage of the ACE DD genotype (60%) in the preeclamptic group was higher than that for the control group (35%); however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260). The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 +/- 5.06 vs 27.6 +/- 3.25 nmol Hip-His Leu(-1) min(-1) mL(-1) in DD control patients; P = 0.0005). Plasma renin activity was markedly reduced in preeclampsia (0.81 +/- 0.2 vs 3.43 +/- 0.8 ng Ang I mL plasma(-1) h(-1) in DD normotensive patients; P = 0.0012). A reduced plasma level of Ang-(1-7) was also observed in preeclamptic women (15.6 +/- 1.3 vs 22.7 +/- 2.5 pg/mL in the DD control group; P = 0.0146). In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.
子痫前期与肾素-血管紧张素系统(RAS)之间的关系目前仍了解甚少。血管紧张素I转换酶(ACE)是RAS的关键组成部分,通过生成血管紧张素II(Ang II)并使血管舒张剂血管紧张素-(1-7)(Ang-(1-7))失活,在血压稳态中发挥重要作用。ACE(I/D)多态性的特征是287 bp片段的插入(I)或缺失(D),导致ACE活性发生变化。在本研究中,ACE(I/D)多态性与子痫前期孕妇(N = 20)和血压正常的孕妇(N = 20)的血浆Ang-(1-7)水平及几种RAS组分相关。子痫前期组中ACE DD基因型的比例(60%)高于对照组(35%);然而,该比例无统计学意义(Fisher精确检验= 2.86,自由度= 2,P = 0.260)。在携带ACE DD基因型的子痫前期女性中观察到最高的血浆ACE活性(58.1±5.06对DD基因型对照组患者的27.6±3.25 nmol Hip-His Leu-1 min-1 mL-1;P = 0.0005)。子痫前期患者的血浆肾素活性显著降低(0.81±0.2对DD基因型血压正常患者的3.43±0.8 ng Ang I mL血浆-1 h-1;P = 0.0012)。子痫前期女性中还观察到血浆Ang-(1-7)水平降低(15.6±1.3对DD基因型对照组的22.7±2.5 pg/mL;P = 0.0146)。相比之下,子痫前期患者的血浆Ang II水平未发生变化。本研究中描述的RAS的选择性变化表明,ACE DD基因型可能用作子痫前期易感性的标志物。