title: Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.
abstract: Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.
authors: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil; Hospital da Lagoa, Endocrinology Sector, Health Ministry, Rio de Janeiro, Brazil.
authors: Ruth
authors: R
authors: Clapauch
authors: Departamento de Bioquímica, IBRAG, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: André Felipe
authors: AF
authors: Mourão
authors: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Anete S
authors: AS
authors: Mecenas
authors: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Priscila A
authors: PA
authors: Maranhão
authors: Departamento de Bioquímica, IBRAG, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Ana
authors: A
authors: Rossini
authors: Laboratory for Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Eliete
authors: E
authors: Bouskela
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D017698:Postmenopause; D012307:Risk Factors
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III