Intracellular signaling controls endothelial cell prostacyclin secretion and regulation of blood clotting time

Venkat Shankarraman, Grace Davis-Gorman, Paul F. McDonagh, Michael Caplan

Research output: Contribution to journalArticle

Abstract

Blood is constantly in contact with a biological material, the blood vessel wall, without the need for anticoagulants to prevent clot formation on the vessel wall; however, manmade biomaterials require anticoagulants to prevent clot formation on the biomaterial. This study seeks to understand how some biomaterials elicit anticoagulant responses from endothelial cells (ECs), whereas others do not. Partial least squares regression analysis was used to correlate the activity of four relevant signaling molecules [extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), Akt, and IκB kinase (IKK)] with human umbilical vein EC secretion of prostacyclin and clotting time of whole blood in contact with these cells. Prostacyclin secretion was increased when JNK activity (mean of all time-points) was elevated and IKK activity at 30 min was reduced. In addition, the clotting time, R-time measured by thromboelastography, was increased (reduced coagulability) when activity of both ERK and JNK (mean of all time-points) were increased and when Akt activity was increased at longer contact times (24-72 h after cell contact with material). Inhibition of each signaling molecule with subsequent testing for prostacyclin secretion and R-time confirmed the interrelationship between EC intracellular signaling and prostacyclin secretion. Generally, JNK inhibition decreased and IKK inhibition increased prostacyclin secretion. Inhibition of ERK or JNK generally increased coagulability, and Akt inhibition decreased the R-time of samples normally eliciting reduced coagulability. These findings increase our understanding of the signaling pathways involved in endothelial prostacyclin release and suggest targets for developing EC-seeded biomaterial surfaces that can minimize coagulation.

Original languageEnglish (US)
Pages (from-to)3374-3383
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume100 A
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Endothelial cells
Epoprostenol
Biomaterials
Blood
Phosphotransferases
Biocompatible Materials
Anticoagulants
Molecules
Blood vessels
Coagulation
Regression analysis
Biological materials
JNK Mitogen-Activated Protein Kinases
Testing

Keywords

  • Biocompatible materials
  • Extracellular matrix
  • Intracellular signaling
  • Systems biology
  • Thrombosis

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

Intracellular signaling controls endothelial cell prostacyclin secretion and regulation of blood clotting time. / Shankarraman, Venkat; Davis-Gorman, Grace; McDonagh, Paul F.; Caplan, Michael.

In: Journal of Biomedical Materials Research - Part A, Vol. 100 A, No. 12, 12.2012, p. 3374-3383.

Research output: Contribution to journalArticle

Shankarraman, Venkat ; Davis-Gorman, Grace ; McDonagh, Paul F. ; Caplan, Michael. / Intracellular signaling controls endothelial cell prostacyclin secretion and regulation of blood clotting time. In: Journal of Biomedical Materials Research - Part A. 2012 ; Vol. 100 A, No. 12. pp. 3374-3383.
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