Estrogen receptor and endothelial dysfunction

Abstract

Estrogen receptor (ER) plays key role on vascular homeostasis. Alterations of ER signaling could conduct to vascular dysfunction, impairment of angiogenesis and platelet aggregation and activation. Preeclampsia (PE) is a pregnancy disease that exhibits these features. We have previously reported that the ER activation by estrone (E1), second natural estrogen, stimulates vasodilators synthesis (NO and PGI2) and inhibits platelet aggregation. This work presents basic (1) and clinical (2) results about the association of ER and vascular dysfunction. 1) Endothelial cells (EC) were incubated with E1 10 nM for 24 h. (2) We tested the existence of association between polymorphisms of ESR1 with PE in a high-risk pregnant women population. Polymorphic variants were studied by RFLP-PCR, employing PvuII and XbaI and resolved by electrophoresis in agarose gels. The in vitro treatment of EC with E1 shows that the hormone stimulated EC growth (91% a/C, p<0.001) and VEGF synthesis. ICI 182780 (ER antagonist), suppressed E1 action. In pregnancy women, the frequencies determined by PvuII was 29% 1(C/T); 59% 2(T/T) and 12% 3(C/C). When XbaI was used the distribution was 35.3% A(A/G); 2% B(A/A) and 62.7% C(G/G). The main haplotype determined was 2C. In contrast, in young women without PE risk the main was 1A.When plasmatic levels of NO were measured, PE pregnant women exhibits a significant reduction in the vasoactive production respect to the whole pregnant population (0.150.024 vs 0.290.040 mM NO/plasma resp.) Results shows that E1 and ER have relevant action on cellular processes involved in endothelial dysfunction. Since the distribution of RE genotypes is different among young women with and without risk of endothelial dysfunction, it could suggest a possible clinical utility of these markers as PE risk predictors.