Abstract 641: Effects of High Salt on the Sexual Dimorphism of Genes Encoding Epigenetic Chromatin Modification Enzymes in the Sprague-dawley Rat Kidney
Young female humans and animals are protected from the development of hypertension and related end-organ damage when compared to age-matched males. We recently showed that high salt (HS) worsened preexisting hypertension and renal injury to a greater extent in Sprague-Dawley (SD) male than female rats. It has been shown that epigenetic modifications can contribute to hypertension and that HS increases the correlation between histone and DNA modifications and gene expression. However, it remains unclear if HS diet is the leading cause of these epigenetic modifications, thereby increasing the predisposition to hypertension. We hypothesize that HS consumption exacerbates sex disparity in the expression of chromatin modification genes, explaining the gender disparity in the susceptibility to hypertension. To test this hypothesis we used SD rats (7±1 week of age), a model of non-sensitive salt hypertension to minimize the influence of genetic susceptibility. We determined the expression levels of chromatin modification genes in male and female rats and the effects of HS diet (8% NaCl for 2-weeks) on the epigenetic changes. We used cDNAs that were prepared from RNA samples extracted from kidney cortexes and PCR array to screen 84 rat epigenetic chromatin modification enzyme genes (RT2 Profiler PCR Array, QIAGEN, Inc, Valencia, CA). Analysis of 9 genes (Aof1, AurkA, AurkB, AurkC, Hdac9, Pak1, Setd6, Smyd3 and Suv420h2) showed different expression levels between sexes, and these were further altered by HS diet. Importantly, the histone deacetylase 9 (Hdac9) gene was expressed significantly higher in the female controls compared to males (p<0.05); however, this difference decreased in response to HS diet. Hdac9 has recently been reported to be associated with a high risk for hypertension. We concluded that in the rat kidney the expression of genes involved in histone modification is sexually dimorphic and these genes are differentially altered by HS diet. Thus, the epigenetic effects of HS consumption may help to explain the mechanisms underlying the sexual disparities in genetic susceptibility to diseases with complex environment-gene interaction, such as hypertension.
- © 2012 by American Heart Association, Inc.