Prognostic value of platelet-derived growth factor in patients with severe sepsis

Growth Factors. 2007 Feb;25(1):15-24. doi: 10.1080/08977190701272784.

Abstract

Primary objective: Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote the structural integrity of the vessel wall and to increase wound healing capacity. Aim of the present study was to determine the role of PDGF-BB in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C (rhAPC) on plasma levels of PDGF-BB in severe sepsis was evaluated as well as the in vitro effect of rhAPC on PDGF-BB-release from human endothelial cells (HUVEC). RESEARCH DESIGN, METHODS AND PROCEDURES: PDGF-BB levels were measured in 46 patients on day 3 of severe sepsis. Twenty-one of these patients received treatment with rhAPC. The in vitro effect of rhAPC on PDGF-BB-messenger RNA synthesis and release of PDGF-BB into supernatants was measured by reverse transcriptase-polymerase chain reaction and ELISA-methods.

Main outcomes and results: Survivors of severe sepsis presented with higher PDGF-BB levels than non-survivors (p < 0.05). Septic patients with PDGF-BB levels below 200 pg/ml were 7.3 times more likely (RR = 7.3, 95% CI: 1.4-44.5; p < 0.05) to die from sepsis than patients with higher PDGF-BB values. RhAPC (1-10 microg/ml) stimulated endothelial PDGF-BB-messenger RNA transcription and PDGF-BB-release in vitro. Plasma levels of PDGF-BB in patients receiving rhAPC were significantly (p < 0.01) higher (median 277.7; 25-75th percentiles: 150.5-414.4 pg/ml) than in patients not treated with rhAPC (median: 125.6; 25-75th percentiles: 55.3-344.7 pg/ml).

Conclusions: The ability of rhAPC to upregulate endothelial PDGF-BB production may represent a new molecular mechanism by which rhAPC controls vessel wall homeostasis and increases tissue healing capacity in severe sepsis. PDGF-BB may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Base Sequence
  • Becaplermin
  • Cells, Cultured
  • DNA Primers / genetics
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Protein C Receptor
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism*
  • Prognosis
  • Protein C / therapeutic use
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / antagonists & inhibitors
  • Recombinant Proteins / therapeutic use
  • Sepsis / blood*
  • Sepsis / drug therapy
  • Sepsis / genetics

Substances

  • Antigens, CD
  • DNA Primers
  • Endothelial Protein C Receptor
  • PROCR protein, human
  • Platelet-Derived Growth Factor
  • Protein C
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Becaplermin
  • drotrecogin alfa activated
  • Platelet Aggregation Inhibitors