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325 Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates

Published online by Cambridge University Press:  19 April 2022

Angelica M. Riojas
Affiliation:
Research Imaging Institute, UT Health San Antonio, San Antonio, Texas, USA
Kimberly D. Spradling-Reeves
Affiliation:
Center for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Robert E. Shade
Affiliation:
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA
Sobha R. Puppala
Affiliation:
Center for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Clinton L. Christensen
Affiliation:
Molecular Services Core, Texas Biomedical Research Institute, San Antonio, Texas, USA
Shifra Birnbaum
Affiliation:
Molecular Services Core, Texas Biomedical Research Institute, San Antonio, Texas, USA
Jeremy P. Glenn
Affiliation:
Molecular Services Core, Texas Biomedical Research Institute, San Antonio, Texas, USA
Cun Li
Affiliation:
Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA
Hossam Shaltout
Affiliation:
Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Shannan Hall-Ursone
Affiliation:
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA
Laura A. Cox
Affiliation:
Center for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA
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Abstract

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OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.

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Valued Approaches
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2022. The Association for Clinical and Translational Science