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Late Onset of Estrogen Therapy Impairs Carotid Function of Senescent Females in Association with Altered Prostanoid Balance and Upregulation of the Variant ERα36
Costa, Tiago Januário (Universidade de São Paulo. Department of Pharmacology)
Jiménez-Altayó, Francesc (Universitat Autònoma de Barcelona. Institut de Neurociències)
Echem, Cinthya (Universidade de São Paulo. Department of Pharmacology)
Akamine, Eliana Hiromi (Universidade de São Paulo. Department of Pharmacology)
Tostes, Rita (Universidade de São Paulo. Department of Pharmacology)
Vila Calsina, Elisabet (Universitat Autònoma de Barcelona. Institut de Neurociències)
Dantas, Ana Paula (Institut d'Investigacions Biomèdiques August Pi i Sunyer. Institut Clínic del Tòrax)
Catelli de Carvalho, Maria Helena (Universidade de São Paulo. Department of Pharmacology)

Data: 2019
Resum: Recent analysis of clinical trials on estrogen therapy proposes the existence of a therapeutic window of opportunity for the cardiovascular benefits of estrogens, which depend on women's age and the onset of therapy initiation. In this study, we aimed to determine how vascular senescence and the onset of estrogen treatment influence the common carotid artery (CCA) function in senescent and non-senescent females. Ovariectomized female senescence-accelerated (SAMP8) or non-senescent (SAMR1) mice were treated with vehicle (OVX) or 17β-estradiol starting at the day of ovariectomy (early-onset, E2E) or 45 days after surgery (late-onset, E2L). In SAMR1, both treatments, E2E and E2L, reduced constriction to phenylephrine (Phe) in CCA [(AUC) OVX: 193. 8 ± 15. 5; E2E: 128. 1 ± 11. 6; E2L: 130. 2 ± 15. 8, p = 0. 004] in association with positive regulation of NO/O2- ratio and increased prostacyclin production. In contrast, E2E treatment did not modify vasoconstrictor responses to Phe in OVX-SAMP8 and, yet, E2L increased Phe vasoconstriction [(AUC) OVX: 165. 3 ± 10; E2E: 183. 3 ± 11. 1; E2L: 256. 3 ± 30. 4, p = 0. 005]. Increased vasoconstriction in E2L-SAMP8 was associated with augmented thromboxane A2 and reduced NO production. Analysis of wild-type receptor alpha (ERα66) expression and its variants revealed an increased expression of ERα36 in E2L-SAMP8 in correlation with unfavorable effects of estrogen in those animals. In conclusion, estrogen exerts beneficial effects in non-senescent CCA, regardless of the initiation of the therapy. In senescent CCA, however, estrogen loses its beneficial action even when administered shortly after ovariectomy and may become detrimental when given late after ovariectomy. Aging and onset of estrogen treatment are two critical factors in the mechanism of action of this hormone in CCA.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès.
Document: article ; recerca ; publishedVersion
Matèria: Estrogen ; Aging ; Estrogen receptor variants ; Cerebrovascular function ; Menopause ; Hormone replacement therapy
Publicat a: Cells, Vol. 8 Núm. 10 (2019) , p. 1-17, ISSN 2073-4409

DOI: 10.3390/cells8101217
PMID: 31597326


17 p, 1.6 MB

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