Human EDN1 ELISA Matched Antibody Pair

The ischemic etiology of heart failure is an independent prognostic factor associated with worse long-term outcome. Recent evidence indicates a role for genetic susceptibility to ischemic heart failure. The authors systematically reviewed all known case-control studies that investigated the association between genetic variants and ischemic heart failure. Twenty-two articles, which examined 24 gene polymorphisms, were identified. In 22 polymorphisms, the variant form had a functional effect. Twenty-two polymorphisms were variants of genes involved in the maladaptive neurohormonal activation. Seven polymorphisms (ACE 1/D, AGT M235T, ADRA2C Del322-325, ADRB2 Arg16Gly, ADRB2 Gln27Glu, EDN1 Lys198Asn, VEGF G-405C) showed a significant association in individual studies. Five polymorphisms (ACE 1/D, ADRB1 Arg389Gly, ADRB2 Argl6Gly, ADRB2 Gln27Glu, TNF G308A) were examined by more than one study, and meta-analyses were performed. The meta-analyses showed no significant sign of heterogeneity. In all settings, there was no significant association, except for polymorphism ADRB2 Arg16Gly under a recessive model (fixed-effects odds ratio = 1.32, 95% confidence interval: 1.05, 1.65). Taking into account that ischemic heart failure is a complex disease with multifactorial etiology, a minor contributing pathogenetic role of the investigated gene polymorphisms cannot be totally excluded. Case-control studies that investigate gene-gene and gene-environment interactions might further elucidate the genetics of ischemic heart failure.

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F-2 alpha (PGF(2 alpha)) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta (p = 0.04) and uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p = 0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF(2 alpha) induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF. Copyright (C) 2006 John Wiley & Sons, Ltd.