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Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis.

Aimes RT, Zijlstra A, Hooper JD, Ogbourne SM, Sit ML, Fuchs S, Gotley DC, Quigley JP, Antalis TM
Thromb Haemost. 2003 89 (3): 561-72

PMID: 12624642 · DOI:10.1267/THRO03030561

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.

MeSH Terms (17)

Acrosin Base Sequence Capillaries Cells, Cultured DNA Primers Endothelium, Vascular Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic GPI-Linked Proteins Humans In Situ Hybridization Kallikreins Membrane Proteins Neovascularization, Physiologic Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Serine Endopeptidases

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