Effect of Tisseel® on expression of tissue plasminogen activator and plasminogen activator inhibitor-1

Michael Peter Diamond, Michael Kruger, Ghassan M. Saed

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective To examine the effect of fibrin sealant on mRNA expression of factors regulating plasminogen activator activity in human peritoneal cells. Plasminogen activator activity is thought to play a pivotal role in degradation of the proteinaceous mass that develops after surgical procedures. Reduction of plasminogen activator activity, as occurs with tissue trauma, results in increased postoperative adhesion development. Design Tissue culture for 6, 12, 24, and 48 hours. Setting University research laboratory. Patients Source of mesothelial cells with fibroblasts. Intervention(s) Measurement of mRNA expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Main outcome measure(s) Multiplex reverse transcriptase/polymerase chain reaction (RT/PCR) was used to determine relative change in t-PA and PAI-1 mRNA levels under six conditions: [1] fibrin sealant (Tisseel®); [2] fibrin sealant (Tisseel®) two components diluted 1:2; [3] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin (a protease inhibitor); [4] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin, both components diluted 1:2; [5] fibrin sealant (Tisseel®) components diluted to physiologic concentrations; and [6] control (culture media). Results The mRNA levels of t-PA and PAI-1 by human peritoneal cells were unchanged during 48 hours. In mesothelial cells, the addition of the compositions increased t-PA mRNA levels. A selective increase was observed in the normal peritoneal fibroblasts at the later time points; similar increases were identified in adhesion fibroblast cultures. In mesothelial cells, the more concentrated compositions generally increased PAI-1 mRNA above control levels, whereas in normal peritoneal fibroblasts PAI-1 levels generally remained unchanged. In contrast, in adhesion fibroblasts, PAI-1 levels decreased over time with treatment. Conclusion(s): Fibrin sealant, in the presence and absence of aprotinin, increases both t-PA and PAI-1 expression by human peritoneal cells; changes not seen with physiologic concentrations of fibrin sealant. These observations suggest that in addition to its ability to help achieve hemostasis, fibrin sealant affects the healing process by altering components of the plasminogen activator system, which may be of benefit in the reduction of postoperative adhesions.

Original languageEnglish (US)
Pages (from-to)1657-1664
Number of pages8
JournalFertility and sterility
Volume81
Issue number6
DOIs
StatePublished - Jun 1 2004

Fingerprint

Fibrin Tissue Adhesive
Plasminogen Activator Inhibitor 1
Tissue Plasminogen Activator
Plasminogen Activators
Fibroblasts
Messenger RNA
Aprotinin
Multiplex Polymerase Chain Reaction
Protease Inhibitors
Hemostasis
Reverse Transcriptase Polymerase Chain Reaction
Human Activities
Culture Media

Keywords

  • Adhesions
  • Tisseel®
  • plasminogen activator activity
  • plasminogen activator inhibitor-1
  • tissue plasminogen activator

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Effect of Tisseel® on expression of tissue plasminogen activator and plasminogen activator inhibitor-1. / Diamond, Michael Peter; Kruger, Michael; Saed, Ghassan M.

In: Fertility and sterility, Vol. 81, No. 6, 01.06.2004, p. 1657-1664.

Research output: Contribution to journalArticle

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abstract = "Objective To examine the effect of fibrin sealant on mRNA expression of factors regulating plasminogen activator activity in human peritoneal cells. Plasminogen activator activity is thought to play a pivotal role in degradation of the proteinaceous mass that develops after surgical procedures. Reduction of plasminogen activator activity, as occurs with tissue trauma, results in increased postoperative adhesion development. Design Tissue culture for 6, 12, 24, and 48 hours. Setting University research laboratory. Patients Source of mesothelial cells with fibroblasts. Intervention(s) Measurement of mRNA expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Main outcome measure(s) Multiplex reverse transcriptase/polymerase chain reaction (RT/PCR) was used to determine relative change in t-PA and PAI-1 mRNA levels under six conditions: [1] fibrin sealant (Tisseel{\circledR}); [2] fibrin sealant (Tisseel{\circledR}) two components diluted 1:2; [3] fibrin sealant (Tisseel{\circledR}) sealer protein component reconstituted without aprotinin (a protease inhibitor); [4] fibrin sealant (Tisseel{\circledR}) sealer protein component reconstituted without aprotinin, both components diluted 1:2; [5] fibrin sealant (Tisseel{\circledR}) components diluted to physiologic concentrations; and [6] control (culture media). Results The mRNA levels of t-PA and PAI-1 by human peritoneal cells were unchanged during 48 hours. In mesothelial cells, the addition of the compositions increased t-PA mRNA levels. A selective increase was observed in the normal peritoneal fibroblasts at the later time points; similar increases were identified in adhesion fibroblast cultures. In mesothelial cells, the more concentrated compositions generally increased PAI-1 mRNA above control levels, whereas in normal peritoneal fibroblasts PAI-1 levels generally remained unchanged. In contrast, in adhesion fibroblasts, PAI-1 levels decreased over time with treatment. Conclusion(s): Fibrin sealant, in the presence and absence of aprotinin, increases both t-PA and PAI-1 expression by human peritoneal cells; changes not seen with physiologic concentrations of fibrin sealant. These observations suggest that in addition to its ability to help achieve hemostasis, fibrin sealant affects the healing process by altering components of the plasminogen activator system, which may be of benefit in the reduction of postoperative adhesions.",
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N2 - Objective To examine the effect of fibrin sealant on mRNA expression of factors regulating plasminogen activator activity in human peritoneal cells. Plasminogen activator activity is thought to play a pivotal role in degradation of the proteinaceous mass that develops after surgical procedures. Reduction of plasminogen activator activity, as occurs with tissue trauma, results in increased postoperative adhesion development. Design Tissue culture for 6, 12, 24, and 48 hours. Setting University research laboratory. Patients Source of mesothelial cells with fibroblasts. Intervention(s) Measurement of mRNA expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Main outcome measure(s) Multiplex reverse transcriptase/polymerase chain reaction (RT/PCR) was used to determine relative change in t-PA and PAI-1 mRNA levels under six conditions: [1] fibrin sealant (Tisseel®); [2] fibrin sealant (Tisseel®) two components diluted 1:2; [3] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin (a protease inhibitor); [4] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin, both components diluted 1:2; [5] fibrin sealant (Tisseel®) components diluted to physiologic concentrations; and [6] control (culture media). Results The mRNA levels of t-PA and PAI-1 by human peritoneal cells were unchanged during 48 hours. In mesothelial cells, the addition of the compositions increased t-PA mRNA levels. A selective increase was observed in the normal peritoneal fibroblasts at the later time points; similar increases were identified in adhesion fibroblast cultures. In mesothelial cells, the more concentrated compositions generally increased PAI-1 mRNA above control levels, whereas in normal peritoneal fibroblasts PAI-1 levels generally remained unchanged. In contrast, in adhesion fibroblasts, PAI-1 levels decreased over time with treatment. Conclusion(s): Fibrin sealant, in the presence and absence of aprotinin, increases both t-PA and PAI-1 expression by human peritoneal cells; changes not seen with physiologic concentrations of fibrin sealant. These observations suggest that in addition to its ability to help achieve hemostasis, fibrin sealant affects the healing process by altering components of the plasminogen activator system, which may be of benefit in the reduction of postoperative adhesions.

AB - Objective To examine the effect of fibrin sealant on mRNA expression of factors regulating plasminogen activator activity in human peritoneal cells. Plasminogen activator activity is thought to play a pivotal role in degradation of the proteinaceous mass that develops after surgical procedures. Reduction of plasminogen activator activity, as occurs with tissue trauma, results in increased postoperative adhesion development. Design Tissue culture for 6, 12, 24, and 48 hours. Setting University research laboratory. Patients Source of mesothelial cells with fibroblasts. Intervention(s) Measurement of mRNA expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Main outcome measure(s) Multiplex reverse transcriptase/polymerase chain reaction (RT/PCR) was used to determine relative change in t-PA and PAI-1 mRNA levels under six conditions: [1] fibrin sealant (Tisseel®); [2] fibrin sealant (Tisseel®) two components diluted 1:2; [3] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin (a protease inhibitor); [4] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin, both components diluted 1:2; [5] fibrin sealant (Tisseel®) components diluted to physiologic concentrations; and [6] control (culture media). Results The mRNA levels of t-PA and PAI-1 by human peritoneal cells were unchanged during 48 hours. In mesothelial cells, the addition of the compositions increased t-PA mRNA levels. A selective increase was observed in the normal peritoneal fibroblasts at the later time points; similar increases were identified in adhesion fibroblast cultures. In mesothelial cells, the more concentrated compositions generally increased PAI-1 mRNA above control levels, whereas in normal peritoneal fibroblasts PAI-1 levels generally remained unchanged. In contrast, in adhesion fibroblasts, PAI-1 levels decreased over time with treatment. Conclusion(s): Fibrin sealant, in the presence and absence of aprotinin, increases both t-PA and PAI-1 expression by human peritoneal cells; changes not seen with physiologic concentrations of fibrin sealant. These observations suggest that in addition to its ability to help achieve hemostasis, fibrin sealant affects the healing process by altering components of the plasminogen activator system, which may be of benefit in the reduction of postoperative adhesions.

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