CCL2 mediates early renal leukocyte infiltration during salt-sensitive hypertension.

American Journal of Physiology. Renal Physiology
Ammar J AlsheikhDavid L Mattson

Abstract

Studies examining mechanisms of Dahl salt-sensitive (SS) hypertension have implicated the infiltration of leukocytes in the kidneys, which contribute to renal disease and elevated blood pressure. However, the signaling pathways by which leukocytes traffic to the kidneys remain poorly understood. The present study nominated a signaling pathway by analyzing a kidney RNA sequencing data set from SS rats fed either a low-salt (0.4% NaCl) diet or a high-salt (4.0% NaCl) diet. From this analysis, chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-C motif) receptor 2 (CCR2) were nominated as a potential pathway modifying renal leukocyte infiltration and contributing to SS hypertension. The functional role of the CCL2/CCR2 pathway was tested by daily administration of CCR2 antagonist (RS-102895 at 5 mg·kg-1·day-1 in DMSO) or DMSO vehicle for 3 or 21 days by intraperitoneal injections during the high salt challenge. Blood pressure, renal leukocyte infiltration, and renal damage were evaluated. The results demonstrated that RS-102895 treatment ameliorated renal damage (urinary albumin excretion; 43.4 ± 5.1 vs. 114.7 ± 15.2 mg/day in vehicle, P < 0.001) and hypertension (144.3 ± 2.2 vs. 158.9 ± 4.8 mmHg in vehicle, P < 0.001) after 21...Continue Reading

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Citations

Jul 30, 2020·American Journal of Hypertension·David L MattsonJustine M Abais-Battad
Jan 27, 2021·International Journal of Molecular Sciences·Carmen De MiguelSantiago Cuevas
Mar 6, 2021·Current Hypertension Reports·Gwendolyn K DavisMeena S Madhur
Sep 17, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Carlos Menendez-CastroKarl F Hilgers

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Methods Mentioned

BETA
RNA-Seq
PCR
ELISA
urine collection
urine collections
flow cytometry
light microscopy

Software Mentioned

BLAST
Core Expression Analysis
Cuffdiff
MetaMorph
IPA
Primer
FlowJo
Cufflinks

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