Cellular and Molecular Life Sciences

, Volume 67, Issue 9, pp 1537–1546

Endogenous protein C is essential for the functional integrity of human endothelial cells

  • Meilang Xue
  • Nikita Minhas
  • Shu-Oi Chow
  • Suat Dervish
  • Philip N. Sambrook
  • Lyn March
  • Christopher J. Jackson
Research Article

DOI: 10.1007/s00018-010-0269-y

Cite this article as:
Xue, M., Minhas, N., Chow, S. et al. Cell. Mol. Life Sci. (2010) 67: 1537. doi:10.1007/s00018-010-0269-y

Abstract

Circulating protein C (PC) plays a vital role as an anti-coagulant and anti-inflammatory mediator. We show here that human endothelial cells produce PC that acts through novel mediators to enhance their own functional integrity. When endogenous PC or its receptor, endothelial protein C receptor (EPCR), was suppressed by small interfering (si) RNA, human umbilical cord endothelial cell (HUVEC) proliferation was decreased and apoptosis elevated. Interestingly, PC or EPCR siRNA significantly increased HUVEC permeability, which is likely via reduction of the angiopoietin (Ang)1/Ang2 ratio and inhibition of the peripheral localization of the tight junction protein, zona occludins-1. In addition, PC or EPCR siRNA inhibited type IV collagen and matrix metalloproteinase-2, providing the first evidence that PC contributes to vascular basement membrane formation. These newly described actions of endogenous PC act to stabilize endothelial cells and enhance barrier function, to potentially promote the functional integrity of blood vessels.

Keywords

Activated protein CEndothelial protein C receptorPermeabilityAngiopoietin

Abbreviations

APC

Activated protein C

EPCR

Endothelial protein C receptor

HUVEC

Human umbilical cord endothelial cells

MMP

Matrix metalloproteinase

siRNA

Small interfering RNA

ZO-1

Zonula occludens-1

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Meilang Xue
    • 1
  • Nikita Minhas
    • 1
  • Shu-Oi Chow
    • 1
  • Suat Dervish
    • 1
  • Philip N. Sambrook
    • 2
  • Lyn March
    • 2
  • Christopher J. Jackson
    • 1
  1. 1.Sutton Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical ResearchThe University of Sydney at Royal North Shore HospitalSt LeonardsAustralia
  2. 2.Department of Rheumatology, Institute of Bone and Joint Research, Kolling Institute of Medical ResearchThe University of Sydney at Royal North Shore HospitalSt LeonardsAustralia