Histone demethylase LSD1 deficiency and biological sex: impact on blood pressure and aldosterone production

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art_HUANG_Histone_demethylase_LSD1_deficiency_and_biological_sex_impact_2019.PDF (894.71 KB)
Citações na Scopus
8
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOSCIENTIFICA LTD
Autores
HUANG, Yuefei
TING, Pei Yee
YAO, Tham M.
HOMMA, Tsuyoshi
BROOKS, Danielle
ADLER, Gail K.
ROMERO, Jose R.
WILLIAMS, Jonathan S.
POJOGA, Luminita H.
Citação
JOURNAL OF ENDOCRINOLOGY, v.240, n.2, p.111-122, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Human risk allele carriers of lysine-specific demethylase 1 (LSD1) and LSD1-deficient mice have salt-sensitive hypertension for unclear reasons. We hypothesized that LSD1 deficiency causes dysregulation of aldosterone's response to salt intake resulting in increased cardiovascular risk factors (blood pressure and microalbumin). Furthermore, we determined the effect of biological sex on these potential abnormalities. To test our hypotheses, LSD1 male and female heterozygote-knockout (LSD1+/-) and WT mice were assigned to two age groups: 18 weeks and 36 weeks. Plasma aldosterone levels and aldosterone production from zona glomerulosa cells studied ex vivo were greater in both male and female LSD1+/- mice consuming a liberal salt diet as compared to WT mice consuming the same diet. However, salt-sensitive blood pressure elevation and increased microalbuminuria were only observed in male LSD1+/- mice. These data suggest that LSD1 interacts with aldosterone's secretory response to salt intake. Lack of LSD1 causes inappropriate aldosterone production on a liberal salt diet; males appear to be more sensitive to this aldosterone increase as males, but not females, develop salt sensitivity of blood pressure and increased microalbuminuria. The mechanism responsible for the cardiovascular protective effect in females is uncertain but may be related to estrogen modulating the effect of mineralocorticoid receptor activation.
Palavras-chave
lysine-specific demethylase 1, sex, blood pressure, aldosterone
URI
https://observatorio.fm.usp.br/handle/OPI/30082
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/16