ADIPONECTIN DIMINISHES ORGAN-SPECIFIC MICROVASCULAR ENDOTHELIAL CELL ACTIVATION ASSOCIATED WITH SEPSIS

Matijs van Meurs*, Pedro Castro, Nathan I. Shapiro, Shulin Lu, Midori Yano, Norikazu Maeda, Tohru Funahashi, Ichiro Shimomura, Jan G. Zijlstra, Grietje Molema, Samir M. Parikh, William C. Aird, Kiichiro Yano

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in mice with endotoxemic challenge and after cecal ligation and puncture compared with healthy control mice. Quantitative reverse transcriptase-polymerase chain reaction for adiponectin reveals a pattern of response that is both model-and organ-specific. When challenged with sepsis, adiponectin deficiency results in increased expression of endothelial adhesion and coagulation molecules in the lung, liver, and kidney as quantified by reverse transcriptase-polymerase chain reaction, increased macrophage and neutrophil infiltration by immunohistochemistry, and vascular leakage in the liver and kidney. Adiponectin-deficient mice have reduced survival following cecal ligation and puncture and increased blood levels of interleukin 6, soluble vascular endothelial growth factor receptor 1, and soluble endothelial adhesion molecules E-selectin and intercellular adhesion molecule 1. Finally, ADPNKO promoted end-organ injury in the liver and kidney, whereas the lungs were not affected. These data suggest a protective role of adiponectin in diminishing microvascular organ-specific endothelial cell activation during sepsis.

Original languageEnglish
Pages (from-to)392-398
Number of pages7
JournalShock
Volume37
Issue number4
DOIs
Publication statusPublished - Apr-2012

Keywords

  • Adiponectin
  • sepsis
  • endothelium
  • multiple organ dysfunction
  • adhesion molecules
  • INTENSIVE-CARE-UNIT
  • SERUM ADIPONECTIN
  • HEMORRHAGIC-SHOCK
  • ADIPOSE-TISSUE
  • GROWTH-FACTOR
  • MICE LACKING
  • MORTALITY
  • EXPRESSION
  • OBESITY
  • HETEROGENEITY

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