title: The Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes are Associated With Different Responses to Salt Intake.
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 gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon MR activation.
  
  
  OBJECTIVE
  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.
  
  
  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 (R sp 0.64; P < 0.0001), NGAL (R sp 0.48; P < 0.0001), HO-1 (R sp 0.53; P < 0.0001), and NF-κB (R sp0.52; 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.
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Alejandra
authors.initials: A
authors.lastname: Tapia-Castillo
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Millenium Institute in Immunology and Immunotherapy, Santiago, Chile;
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Millenium Institute in Immunology and Immunotherapy, Santiago, Chile;
authors.forename: Carmen
authors.initials: C
authors.lastname: Campino
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Caroline
authors.initials: C
authors.lastname: Hill
authors.affiliation: Servicios de Laboratorios Clinicos, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Fidel
authors.initials: F
authors.lastname: Allende
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Millenium Institute in Immunology and Immunotherapy, Santiago, Chile;
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchiola
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Carmen
authors.initials: C
authors.lastname: Carrasco
authors.affiliation: Pediatrics, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bancalari
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Carolina
authors.initials: C
authors.lastname: Valdivia
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Carlos
authors.initials: C
authors.lastname: Lagos
authors.affiliation: Pediatrics, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martinez-Aguayo
authors.affiliation: Pediatrics, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Hernan
authors.initials: H
authors.lastname: Garcia
authors.affiliation: Pediatrics, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Marlene
authors.initials: M
authors.lastname: Aglony
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile;
authors.forename: Rene F
authors.initials: RF
authors.lastname: Baudrand
authors.affiliation: Millenium Institute in Immunology and Immunotherapy, Santiago, Chile; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas. Pontificia Universidad Católica de Chile, Santiago, Chile;
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.affiliation: Millenium Institute in Immunology and Immunotherapy, Santiago, Chile; Laboratory of Integrative Physiology, ICBM, Universidad de Chile, Santiago, Chile;
authors.forename: Luis F
authors.initials: LF
authors.lastname: Michea
authors.affiliation: Millenium Institute in Immunology and Immunotherapy, Santiago, Chile; Departamento de Ciencias Biológicas, Facultad Ciencias Biológicas y Facultad de Medicina Universidad Andrés Bello, Santiago, Chile.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Riedel
authors.affiliation: Endocrinology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Millenium Institute in Immunology and Immunotherapy, Santiago, Chile; cfardella@med.puc.cl.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D020830:rac1 GTP-Binding Protein
keywords: PBMC; RAC1; blood pressure; essential hypertension; gene expression; hypertension; salt intake.