Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension

Sonu Kashyap, Mazen Osman, Christopher M. Ferguson, Meryl C. Nath, Bhaskar Roy, Karen R. Lien, Karl A Nath, Vesna D Garovic, Lilach O Lerman, Joseph Peter Grande

Research output: Contribution to journalArticle

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Abstract

Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.

Original languageEnglish (US)
Article number8598
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Renovascular Hypertension
Knockout Mice
Kidney
Wounds and Injuries
Renal Artery Obstruction
Atrophy
Magnetic Resonance Imaging
Inflammation
Inflammation Mediators
Renal Circulation
Surgical Instruments
Fibrosis
Cardiovascular Diseases
Perfusion
Oxygen

ASJC Scopus subject areas

  • General

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Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension. / Kashyap, Sonu; Osman, Mazen; Ferguson, Christopher M.; Nath, Meryl C.; Roy, Bhaskar; Lien, Karen R.; Nath, Karl A; Garovic, Vesna D; Lerman, Lilach O; Grande, Joseph Peter.

In: Scientific Reports, Vol. 8, No. 1, 8598, 01.12.2018.

Research output: Contribution to journalArticle

Kashyap, Sonu ; Osman, Mazen ; Ferguson, Christopher M. ; Nath, Meryl C. ; Roy, Bhaskar ; Lien, Karen R. ; Nath, Karl A ; Garovic, Vesna D ; Lerman, Lilach O ; Grande, Joseph Peter. / Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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