title: Pro-Apoptotic Effects of Plasma from Patients with Cardiorenal Syndrome on Human Tubular Cells.
abstract: BACKGROUND
  The pathophysiology of Cardiorenal Syndrome Type 1 (CRS1) is widely studied, although the mechanisms by which renal tubular epithelial cells (TECs) cease to proliferate and embark upon terminal differentiation, following the initial insult of heart failure (HF), remain a key target. This study seeks to provide insight into the pathophysiological pathways in CRS1; we evaluated in vitro the effects of CRS1 plasma on TECs.
  
  
  METHODS
  We enrolled 40 acute HF patients and 15 controls (CTR) without HF or acute kidney injury (AKI). Ten out of 40 HF patients exhibited AKI at the time of admission for HF or developed AKI during hospitalization and were classified as CRS1. In vitro, cell viability, DNA fragmentation and caspase-3 levels were investigated in TECs incubated with HF, CRS1, and CTR plasma. We assessed inflammatory cytokines and NGAL expression at the gene and protein levels.
  
  
  RESULTS
  We observed a marked pro-apoptotic activity and a significantly increased in vitro level of apoptosis in TECs incubated with plasma from CRS1 patients compared to HF and CTR (p < 0.01). In the CRS1 group, the mRNA expression of IL-6, IL-18 and NGAL resulted significantly higher in TECs incubated with CRS1 plasma compared with those incubated with plasma from HF and CTR (p < 0.01). IL-6, IL-18, NGAL, and RANTES levels were significantly higher in TECs supernatant incubated with CRS1 plasma compared with HF patients and CTR plasma (p < 0.01).
  
  
  CONCLUSIONS
  In vitro exposure to plasma from CRS1 patients altered the expression profile of TECs characterized by increases in proinflammatory mediators, release of tubular damage markers, and apoptosis.
authors.affiliation: Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Virzì
authors.forename: Massimo
authors.initials: M
authors.lastname: de Cal
authors.forename: Sonya
authors.initials: S
authors.lastname: Day
authors.forename: Alessandra
authors.initials: A
authors.lastname: Brocca
authors.forename: Dinna N
authors.initials: DN
authors.lastname: Cruz
authors.forename: Chiara
authors.initials: C
authors.lastname: Castellani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: Chiara
authors.initials: C
authors.lastname: Bolin
authors.forename: Marny
authors.initials: M
authors.lastname: Fedrigo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vescovo
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood*; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D059347:Cardio-Renal Syndrome / Q000097:blood*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010949:Plasma; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D018946:Chemokine CCL5; D020382:Interleukin-18; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D053148:Caspase 3