ESPE Abstracts (2015) 84 FC1.3

Aldosterone and Mineralocorticoid Receptor as Inducers of Immune Markers in Peripheral Blood Mononuclear Cells: Beyond Elevating Blood Pressure

Andrea Vecchiolaa, Natalia Muñoz-Durangod, Mariana Cifuentesc, Carlos Lagosa, Cristóbal Fuentesa, Luis-Martín Gonzáleza, David Ortiza, Cristian Carvajala, Alejandra Tapia-Castilloa, Carolina Valdiviaa, Alejandro Martínez-Aguayoa, Fidel Allendeb, Sandra Solarib, Rodrigo Bancalaria, Hernán Garcíaa, Carmen Campinoa, René Baudranda, Alexis Kalergisd & Carlos E Fardellaa,d

aMolecular Endocrinology Laboratory, Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; bDepartment of Clinical Laboratories, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; cInstitute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile; dMillennium Institute of Immunology and Immunotherapy, Santiago, Chile

Background: In vitro studies suggest a broader role for aldosterone, beyond elevating blood pressure. Clinical data support the notion that aldosterone can directly alter the function of the immune system and can participate in low-grade inflammation which leads to blood pressure elevation and end organ damage.

Objective and hypothesis: To assess in humans, whether aldosterone plasma levels and mineralocorticoid receptor (MR) expression associate with immunological markers in peripheral blood mononuclear cells (PBMCs).

Methods: We recruited 228 subjects (11-67 years, BMI 27.09±4.8 kg/m2, 61% female). We measured in blood samples: aldosterone, hsCRP, and IL17. Sodium was measured in serum and urine. We isolated mRNA from PBMCs and evaluated MR, pathogen-activated molecular patterns (PAMPs like TLR-4, TLR-2, CD-14), damage-activated molecular patterns (DAMPs like Hsp-90, NGAL) and IL17 expression by q-RT-PCR. Statistics was done by Spearman.

Results: Aldosterone plasma levels were directly associated to CD-14 mRNA expression (r=0.2998 P=0.0022) and inversely associated with age (r=−0.2904 P<0.00001), Na_S (r=−0.2150 P=0.0011) and Na_U (r=−0.1995 P=0.0025). There was no association with hsCRP, TLR-4, TLR-2 nor DAMPs expression. Neither did IL17 levels or expression. MR mRNA expression in PBMCs was directly associated to IL17 levels (r=0.2459 P=0.0217) and IL17 expression (r=0.4472 P=0.0002). It was also directly associated to CD-14 (r=0.6769 P<0.0001) and NGAL (r=0.3216 P=0.0024) expression, and inversely associated to Hsp-90 (r=−0.2591 P=0.0258) expression. There was no association with TLR-2, TLR-4 expression neither hsCRP levels.

Conclusion: Aldosterone plasma levels and/or MR-expression in PBMCs are associated to PBMC inflammatory activation markers, which could predispose to autoimmune disorder development.

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