Role of inflammation in the pathogenesis of cardiorenal syndrome in a rat myocardial infarction model

Eunjung Cho, Mina Kim, Yoon Sook Ko, Hee Young Lee, Myeongjin Song, Myung Gyu Kim, Hyoung Kyu Kim, Won Yong Cho, Sang Kyung Jo

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background. Cardiorenal syndrome is now frequently recognized, and the combined dysfunction of heart and kidney increases morbidity and mortality. This study aimed to investigate possible mechanisms that underlie renal damage following heart dysfunction using a rat myocardial infarction model, focusing on the inflammatory pathway. Methods. Rats were randomized into four groups: normal, volume depletion, sham operation and myocardial infarction (MI). MI was induced by the ligation of the left coronary artery and a volume depletion model was produced by low-salt diet and furosemide injection. Biochemical, histological and flow cytometric analyses were performed at 3 days and 4 and 8 weeks after MI. Results. On Day 3 following MI, the development of subclinical acute kidney injury was identified through significantly increased serum and urine neutrophil gelatinase-associated lipocalin level. We detected the increase of activated monocytes (CC chemokine receptor 2+ ED-1+) in peripheral blood, along with the infiltration of ED-1+ macrophages and the increment of nuclear p65 in the kidney of MI rats, suggesting the contribution of nuclear factor-kappa B-mediated inflammation in the development of Type 1 cardiorenal syndrome (CRS). The inflammatory cytokines, interleukin-6 and tumour necrosis factor-α (TNF-α) mRNA expression, as well as microvascular endothelial permeability and tubular cell apoptosis, significantly increased in the kidneys of MI rats. At 4 and 8 weeks after MI, tubular cell apoptosis, ED-1+ macrophage infiltration and interstitial fibrosis increased in MI rats, and these chronic changes were significantly mitigated by systemic monocyte/macrophage depletion using liposome clodronate. Conclusion. This study identifies the possible important role of inflammatory response as a mediator of heart-kidney crosstalk in CRS.

Original languageEnglish
Pages (from-to)2766-2778
Number of pages13
JournalNephrology Dialysis Transplantation
Volume28
Issue number11
DOIs
Publication statusPublished - 2013 Nov 1

Keywords

  • Inflammation
  • Kidney
  • Myocardial infarction

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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