INVESTIGADORES
SCHUMAN Mariano Luis
artículos
Título:
Valproate Decreases Transgenerationally Blood Pressure by Affecting Thyrotropin-releasing Hormone Promoter DNA Methylation and Gene Expression in Spontaneously Hypertensive Rat
Autor/es:
LANDA, MARÍA SILVINA; SCHUMAN, MARIANO LUIS; AISICOVICH, MAIA; PERES DIAZ, LUDMILA SOLEDAD; MARIELA M. GIRONACCI; SILVIA INES GARCIA; PIROLA, CARLOS JOSÉ
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2024
ISSN:
0300-8177
Resumen:
Central TRH, a neuropeptide, is involved incardiovascular regulation. We demonstrated that the overexpression of diencephalicTRH (dTRH) in SHR rats can be prevented by antisense treatment, normalizingblood pressure (BP). Valproate (VPA) is an inhibitor of histone deacetylases(HDAC) which modulates gene expression through epigenetic modifications such asDNA methylation. Aims: Study the role of HDAC inhibition in the regulation of dTRHgene expression and its effect on the pathogenesis of hypertension. Mainmethods: We treated 7-weeks-old male and female SHR and WKY rats with VPA for10 weeks and evaluated BP, dTRH mRNA and methylation gene status. Key findings:VPA attenuated the elevated BP and dTRH mRNA expression characteristic of SHR. Indeed,we found a significant 62% reduction in dTRH mRNA expression in the SHR+VPAgroup compared to control SHR. The decrease TRH mRNA expression induced by VPAwas confirmed in vitro in a primary neuron culture using trichostatin A. Withmethylation specific PCR we demonstrated a significant increase in TRH promoterDNA methylation level in SHR+VPA group compared to control SHR. Also there was asignificant negative correlation between methylation status, dTRH mRNAexpression, and blood pressure values. After 2 weeks of treatment interruption,rats were mated. Although they did not received any treatment, the offspringborn from VPA-treated SHR parents showed similar changes in BP, dTRH expressionand methylation status, implying a transgenerational inheritance. Our findingssuggest that dTRH modulation by epigenetics mechanism affects BP and could beinherited by the next generation in SHR rats.
