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- Steinthorsdottir, V, et al.
(författare)
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Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5976-
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
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- Scott, G. D., et al.
(författare)
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Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.
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- Cruz, MN, et al.
(författare)
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Acute responses to phytoestrogens in small arteries from men with coronary heart disease
- 2006
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 290:5, s. H1969-H1975
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-α (ERα) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERβ agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERα agonist) were determined. These were compared with responses to reference compound 17β-estradiol (17β-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nω-nitro-l-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17β-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17β-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.
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- Cruz, MN, et al.
(författare)
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Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-beta knockout mice
- 2006
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 290:2, s. H823-H829
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this study were to determine whether acute dilatory responses to estrogen receptor agonists are altered in isolated arteries from estrogen receptor β-deficient mice (β-ERKO) and to gain insight into the role of nitric oxide (NO) in these responses. Femoral arteries (∼250 μm) from male and female β-ERKO mice and wild-type (WT) littermates (26 female, 13 in each group; and 24 male, 12 in each group) were mounted on a Multi-Myograph. Concentration-response curves to 17β-estradiol (17β-E2) and the selective estrogen receptor-α (ER-α) agonist propyl-[1H]-pyrazole-1,3,5-triy-trisphenol (PPT) were obtained before and after NO synthase (NOS) inhibition [ Nω-nitro-l-arginine methyl ester (l-NAME), 0.1 mM] in arteries preconstricted with U-46619 (a thromboxane analog). In WT mice, responses to the potent estrogen receptor-β (ER-β) agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and the contribution of NO were also assessed. Concentration-response curves to 17β-E2and PPT were similar in arteries from WT and β-ERKO mice of both genders, but NO-mediated relaxation was different, since l-NAME reduced 17β-E2mediated relaxation in arteries from male and female β-ERKO but not WT mice ( P < 0.05). NOS inhibition reduced dilation to PPT in arteries from male and female WT mice, as well as arteries from female β-ERKO mice ( P < 0.05). Responses to DPN in arteries from WT female and male mice did not differ after NOS inhibition. The acute dilatory responses to estrogenic compounds are similar in WT and β-ERKO mice but differ mechanistically. Because NO appeared to contribute to responses to 17β-E2in arteries from β-ERKO but not WT mice, the presence of ER-β apparently inhibits ER-α-mediated NO relaxation.
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- Douglas, G, et al.
(författare)
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Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor-beta knockout mouse
- 2008
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 294:1, s. R112-R120
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Tidskriftsartikel (refereegranskat)abstract
- The role of the estrogen receptor (ER) subtypes in the modulation of vascular function is poorly understood. The aim of this study was to characterize ex vivo the functional properties of small arteries and their response to estrogens in the mesenteric circulation of female and male ER-β knockout mice (β-ERKO) and their wild-type (WT) littermates. Responses to changes in intraluminal flow and pressure were obtained before and after incubation with 17β-estradiol or ER-α agonist propyl-pyrazole-triol (3 h; 10 nM). Cumulative concentration-response curves to acetylcholine, norepinephrine, and passive distensibility were compared with respect to sex and genotype. The collagen and elastin content within the vascular wall and ER expression were also determined. Endothelial morphology was visualized by scanning electron microscopy. 17β-Estradiol and propyl-pyrazole-triol-treated arteries from female β-ERKO and WT mice showed enhanced flow-mediated dilation, but this was not evident in males. Distensibility was decreased in arteries from β-ERKO females. Sex differences in myogenic tone were observed in 17β-estradiol-treated arteries, but were similar between β-ERKO and WT mice. Acetylcholine- and norepinephrine-induced responses were similar between groups and sexes. ER-α was similarly expressed in the endothelium and media of arteries from all groups studied, as well as ER-β in WT animals. Endothelial morphology was similar in arteries from animals of both sexes and genotype; however, arterial elastin content was decreased, and collagen content was increased in β-ERKO male compared with WT male and with β-ERKO female. We suggest that ERs play a sex-specific role in estrogen-mediated flow responses and distensibility, and that deletion of ER-β affects artery structure but only in male animals. Further studies in β-ERKO mice with established hypertension and in α-ERKO mice are warranted.
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