The expression of RAC1 and mineralocorticoid pathway-dependent genes are associated with different responses to salt intake

Alejandra Tapia-Castillo, Cristian A. Carvajal, Carmen Campino, Caroline Hill, Fidel Allende, Andrea Vecchiola, Carmen Carrasco, Rodrigo Bancalari, Carolina Valdivia, Carlos Lagos, Alejandro Martinez-Aguayo, Hernan Garcia, Marlene Aglony, Rene F. Baudrand, Alexis M. Kalergis, Luis F. Michea, Claudia A. Riedel, Carlos E. Fardella

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8 Citations (Scopus)

Abstract

Background Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO- 1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinaseassociated lipocalin (NGAL), a cytokine upregulated upon MR activation. aim We evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-κB expression, mineralo- and glucocorticoids levels, and inflammatory parameters. subjects and methods We studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-κB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein. results We identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-κB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (Rsp 0.64; P < 0.0001), NGAL (Rsp 0.48; P < 0.0001), HO-1 (Rsp 0.53; P < 0.0001), and NF-κB (Rsp0.52; P < 0.0001). We did not identify any association between RAC1 and clinical or biochemical variables. conclusions RAC1 expression was associated with an increase in MR, NGAL, NF-κB, and HO-1 expression, suggesting that RAC1 could be a mediator of cardiovascular damage induced by sodium, and may also useful to identify subjects with different responses to salt intake.

Original languageEnglish
Pages (from-to)722-728
Number of pages7
JournalAmerican Journal of Hypertension
Volume28
Issue number6
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Blood pressure
  • Essential hypertension
  • Gene expression
  • Hypertension
  • PBMC
  • RAC1
  • Salt intake

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Tapia-Castillo, A., Carvajal, C. A., Campino, C., Hill, C., Allende, F., Vecchiola, A., Carrasco, C., Bancalari, R., Valdivia, C., Lagos, C., Martinez-Aguayo, A., Garcia, H., Aglony, M., Baudrand, R. F., Kalergis, A. M., Michea, L. F., Riedel, C. A., & Fardella, C. E. (2015). The expression of RAC1 and mineralocorticoid pathway-dependent genes are associated with different responses to salt intake. American Journal of Hypertension, 28(6), 722-728. https://doi.org/10.1093/ajh/hpu224