title: Role of inflammation in the pathogenesis of cardiorenal syndrome in a rat myocardial infarction model.
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.
  
  
  CONCLUSIONS
  This study identifies the possible important role of inflammatory response as a mediator of heart-kidney crosstalk in CRS.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Korea University Anam Hospital, Seoul, South Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Cho
authors.forename: Mina
authors.initials: M
authors.lastname: Kim
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Ko
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Song
authors.forename: Myung Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Hyoung-Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Won-Yong
authors.initials: WY
authors.lastname: Cho
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D059347:Cardio-Renal Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000503:physiopathology*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D016207:Cytokines; D054834:Lipocalins; D012333:RNA, Messenger
keywords: inflammation; kidney; myocardial infarction