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Thromb Haemost 2003; 89(03): 561-572
DOI: 10.1055/s-0037-1613388
Vascular Development and Vessel Remodelling
Schattauer GmbH

Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis

Ronald T. Aimes
1   Department of Cell Biology, The Scripps Research Institute, La Jolla, California
,
Andries Zijlstra
1   Department of Cell Biology, The Scripps Research Institute, La Jolla, California
,
John D. Hooper
1   Department of Cell Biology, The Scripps Research Institute, La Jolla, California
,
Steven M. Ogbourne
2   Cancer Metastasis Laboratory, University of Queensland and the Queensland Institute of Medical Research, Brisbane, Queensland, Australia
,
Mae-Le Sit
2   Cancer Metastasis Laboratory, University of Queensland and the Queensland Institute of Medical Research, Brisbane, Queensland, Australia
,
Simone Fuchs
2   Cancer Metastasis Laboratory, University of Queensland and the Queensland Institute of Medical Research, Brisbane, Queensland, Australia
,
David C. Gotley
3   Department of Surgery, Princess Alexandra Hospital, Queensland, Australia
,
James P. Quigley
1   Department of Cell Biology, The Scripps Research Institute, La Jolla, California
,
Toni M. Antalis
2   Cancer Metastasis Laboratory, University of Queensland and the Queensland Institute of Medical Research, Brisbane, Queensland, Australia
4   Department of Vascular Biology, The Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland, USA
› Author Affiliations Financial support: This work was supported in part by National Institutes of Health Grants R01 CA65660 and P01 HL31950 (to J. P. Q.), a NIH Training Grant T32 HL07695 (to A. Z.), and by the National Health and Medical Research Council of Australia with a grant to T. M. A., and a C. J. Martin/R. G. Menzies Fellowship (138722) (to J. D. H.). Contributing authors: The authors R. T. Aimes, A. Zijlstra, and J. D. Hooper contributed equally to this work. J. P. Quigley, T. M. Antalis supported and contributed equally to this work and should be considered joint corresponding authors.
Further Information

Publication History

Received 20 November 2002

Accepted after revision 27 December 2002

Publication Date:
09 December 2017 (online)

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Summary

Many serine proteases play important regulatory roles in complex biological systems, but only a few have been linked directly with capillary morphogenesis and angiogenesis. Here we provide evidence that serine protease activities, independent of the plasminogen activation cascade, are required for microvascular endothelial cell reorganization and capillary morphogenesis in vitro. A homology cloning approach targeting conserved motifs present in all serine proteases, was used to identify candidate serine proteases involved in these processes, and revealed 5 genes (acrosin, testisin, neurosin, PSP and neurotrypsin), none of which had been associated previously with expression in endothelial cells. A subsequent gene-specific RT-PCR screen for 22 serine proteases confirmed expression of these 5 genes and identified 7 additional serine protease genes expressed by human endothelial cells, urokinase-type plasminogen activator, protein C, TMPRSS2, hepsin, matriptase/ MT-SP1, dipeptidylpeptidase IV, and seprase. Differences in serine protease gene expression between microvascular and human umbilical vein endothelial cells (HUVECs) were identified and several serine protease genes were found to be regulated by the nature of the substratum, ie. artificial basement membrane or fibrillar type I collagen. mRNA transcripts of several serine protease genes were associated with blood vessels in vivo by in situ hybridization of human tissue specimens. These data suggest a potential role for serine proteases, not previously associated with endothelium, in vascular function and angiogenesis.

Keywords

Serine protease - endothelial cell - tubule morphogenesis - micro-vascular - angiogenesis
 

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