Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood vessel growth by angiogenesis plays an essential role in embryonic development, wound healing, and tumor growth. To understand the molecular cues underlying this process we have used the PCR-based subtractive hybridization method, representational difference analysis, to identify genes upregulated in endothelial cells (EC) forming tubes in 3D collagen gels, compared to migrating and proliferating cells in 2D cultures. We identified several previously characterized angiogenic markers, including the alpha(v) chain of the alpha(v)beta3 integrin and plasminogen activator inhibitor-1, suggesting overlap in gene expression between tube-forming cells in vitro and in vivo. We also found a 2- to 10-fold upregulation of (beta)ig-h3 (a collagen-binding extracellular matrix protein), NrCAM (a "neural" cell adhesion molecule), Annexin II (a tPA receptor), ESM-1 (an EC-specific molecule of unknown function), and Id2 (an inhibitory bHLH transcription factor). We identified a novel splice variant of the ESM-1 gene and also detected dramatically enhanced expression of ESM-1 and (beta)ig-h3 in several tumors. Antisense oligonucleotides to (beta)ig-h3 blocked both gene expression and tube formation in vitro, suggesting that (beta)ig-h3 may play a critical role in EC-matrix interactions. These data expand the suite of genes implicated in vascular remodeling and angiogenesis.
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PMID:Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM. 1186 39

The aim of this study was to develop and validate the novel microLC/MS-MRM method for the simultaneous quantification of six proteins: angiopoietin 2 (Angpt-2), soluble form of fms-like tyrosine kinase 1 (sFLT-1), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA), endocan (ESM-1), soluble form of E-selectin (sE-sel), and one peptide: adrenomedullin (ADM) in mouse plasma. Two approaches were compared: a stable isotope dilution (SID) method- used as a reference and a modified SID (mSID) procedure. In SID strategy the calibration curves were used, whereas in mSID the ratio between the chromatogram peak area of endogenous tryptic peptides at unknown concentration to chromatogram peak area of exogenous, stable isotope-labelled internal standards (SISs) added to the sample at known concentration was calculated. The microLC/MS-MRM method in the SID approach was linear from 0.250 pmol/mL to 250 pmol/mL for Angpt-2; 5 pmol/mL to 5000 pmol/mL for sFLT-1; 2.5 pmol/mL to 5000 pmol/mL for PAI-1; 0.375 pmol/mL to 250 pmol/mL for t-PA; 0.375 pmol/mL to 187.5 pmol/mL for ESM-1; 2.5 pmol/mL to 5000 pmol/mL for sE-sel and 0.375 pmol/mL to 250 pmol/mL for ADM. LPS-induced changes in plasma assessed based on SID and mSID approaches gave comparable quantitative results and featured LPS-induced dysregulation of endothelial permeability (Angpt-2, sFLT-1), glycocalyx injury (SDC-1) accompanied by a pro-thrombotic response (PAI-1). In addition, we applied microLC/MS-MRM method with mSID strategy to analyze human plasma samples from patients with chronic myeloid leukemia (CML) and obstructive sleep apnoea (OSA) and demonstrated usefulness of the method to characterize endothelial function in humans. In conclusion, the microLC/MS-MRM method with mSID strategy applied for simultaneous quantification of protein biomarkers of endothelial function in plasma represents a novel targeted proteomic platform for the comprehensive evaluation of endothelial function in mice and humans.
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PMID:Quantitative measurement of selected protein biomarkers of endothelial dysfunction in plasma by micro-liquid chromatography-tandem mass spectrometry based on stable isotope dilution method. 3060 7