Conference Abstract| January 01 2003 Nicotine Abolishes the Hypoxic Induction of Vegf in Human Microvascular Endothelial Cells Martin Griffiths; Martin Griffiths 1Department of Surgery Royal Free Hospital London Search for other works by this author on: This Site PubMed Google Scholar Richard Stratum; Richard Stratum 2Centre for Rheumatology - Royal Free Hospital London Search for other works by this author on: This Site PubMed Google Scholar David Abraham; David Abraham 2Centre for Rheumatology - Royal Free Hospital London Search for other works by this author on: This Site PubMed Google Scholar Richard Siow; Richard Siow 3Vascular Biology Research Centre — King's College London Search for other works by this author on: This Site PubMed Google Scholar Jeremy Pearson; Jeremy Pearson 3Vascular Biology Research Centre — King's College London Search for other works by this author on: This Site PubMed Google Scholar Daryll Baker; Daryll Baker 1Department of Surgery Royal Free Hospital London Search for other works by this author on: This Site PubMed Google Scholar Carol Black Carol Black 2Centre for Rheumatology - Royal Free Hospital London Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8736 Print ISSN: 0143-5221 © 2003 The Biochemical Society and the Medical Research Society2003 Clin Sci (Lond) (2003) 104 (s48): 2P. https://doi.org/10.1042/cs104002Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Martin Griffiths, Richard Stratum, David Abraham, Richard Siow, Jeremy Pearson, Daryll Baker, Carol Black; Nicotine Abolishes the Hypoxic Induction of Vegf in Human Microvascular Endothelial Cells. Clin Sci (Lond) 1 January 2003; 104 (s48): 2P. doi: https://doi.org/10.1042/cs104002Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 2003 The Biochemical Society and the Medical Research Society2003 Article PDF first page preview Close Modal You do not currently have access to this content.

Background: Endothelin-1 (ET-1) is a 21 amino acid peptide with vasoconstrictor and mitogenic properties. We observed that ET-1 is expressed around areas of angiogenesis in ischaemic skeletal muscle, and sought to determine whether ET-1 provides an angiogenic stimulus to human microvascular cells. Methods: Human dermal microvascular cells (HMEC-1) were grown on growth factor reduced Matrigel, with or without ET-1 at various concentrations. Synergy with the angiogenic factor vascular endothelial growth factor (VEGF) was sought by co-adding ET-1 with VEGF. In addition, we measured the effects of selective inhibitors of the ET-1 receptor. Angiogenesis was measured after 24-h treatment by visual analysis of microvessel growth and by scanning the mean optical density of images of the angiogenic field. Results: ET-1 enhanced angiogenesis in the presence of VEGF (P < 0.02). The ET(B) receptor antagonist BQ788 suppressed angiogenesis below basal levels (P < 0.04), whereas the ET(A) receptor antagonist had no effect. Microvascular cells were found to release ET-1 when grown on Matrigel, with enhancement following treatment with VEGF. Conclusions: These data suggest that in human microvascular cells, ET-1 is an important autocrine growth factor, acting downstream and in concert with VEGF to stimulate angiogenesis. We suggest that the mitogenic properties of ET-1 are ET(B) mediated, unlike the effects on vascular tone, which are ET(A) mediated. The separation of these effects might provide benefit to patients with peripheral vascular disease, where selective ET(A) receptor antagonists could promote vasodilatation whilst preserving the ET(B) mediated angiogenic effects.