The role of the renin–angiotensin–aldosterone system in preeclampsia: genetic polymorphisms and microRNA

Abstract

The compensatory alterations in the rennin-angiotensin-aldosterone system (RAAS) contribute to the salt-water balance and sufficient placental perfusion for the subsequent well-being of the mother and fetus during normal pregnancy and is characterized by an increase in almost all the components of RAAS. Preeclampsia, however, breaks homeostasis and leads to a disturbance of this delicate equilibrium in RAAS both for circulation and the uteroplacental unit. Despite being a major cause for maternal and neonatal morbidity and mortality, the pathogenesis of preeclampsia remains elusive, where RAAS has been long considered to be involved. Epidemiological studies have indicated that preeclampsia is a multifactorial disease with a strong familial predisposition regardless of variations in ethnic, socioeconomic, and geographic features. The heritable allelic variations, especially the genetic polymorphisms in RAAS, could be the foundation for the genetics of preeclampsia and hence are related to the development of preeclampsia. Furthermore, at a posttranscriptional level, miRNA can interact with the targeted site within the 3 0 -UTR of the RAAS gene and thereby might participate in the regulation of RAAS and the pathology of preeclampsia. In this review, we discuss the recent achievements of genetic polymorphisms, as well as the interactions between maternal and fetal genotypes, and miRNA posttranscriptional regulation associated with RAAS in preeclampsia. The results are controversial but utterly inspiring and attractive in terms of potential prognostic significance. Although many studies suggest positive associations with genetic mutations and increased risk for preeclampsia, more meticulously designed large-scale investigations are needed to avoid the interference from different variations.

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

“…Among them are the polymorphisms in genes that are involved in blood pressure regulation through the renin-angiotensin-aldosterone system. Polymorphisms in this system are associated with hypertensive disorders in pregnancy as was reported for the white population of Poland [39], and the black Afro-Caribbean, but not the white Europeans in South and Central London [9]. However, this was not the case among Asian women of Taiwan [9].…”

“…Polymorphisms were already identified in various genes that are involved in different functions related to the PE disorder [9–14]. Among them are the polymorphisms in genes that are involved in blood pressure regulation through the renin-angiotensin-aldosterone system.…”

“…Single nucleotide polymorphisms (SNPs) have been identified as risk factors for PE leading to gestational hypertension [9], vasodilatation [10], angiogenesis regulation [11], interleukin-related inflammation [12], and human placental diseases [13, 14]. Affected pathways include: impaired placentation [15], immune-fetal rejection [16], anti-angiogenic state [17], and various cardiovascular disorders [18, 19].…”

Angiotensin Converting Enzyme 90kDa isoform: Biomarker for diagnosis of preeclampsia?

“…The renin-angiotensin system (RAS), responsible for the regulation of blood pressure and electrolyte homeostasis, has been actively investigated in PES [25,26]. Studies on the genetic polymorphism of the angiotensin-converting enzyme (ACE), one of the components of the RAS, demonstrate that the D allele is related to elevated plasma ACE levels, and is strongly associated with cardiovascular diseases [27].…”

Angiotensin II type 1 receptor autoantibody as a novel regulator of aldosterone independent of preeclampsia

“…A decreased level of aldosterone (ALD), one of the most important hemodynamic-regulatory hormones for plasma volume, and the resulting inadequate plasma volume expansion during pregnancy are involved in preeclampsia. Impaired ALD synthesis precedes manifestation of clinical preeclampsia [9], correlates with preeclampsia severity, and restricts circulatory volume expansion, resulting in increased blood pressure and protein excretion [10].…”