gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Hyaluronic acid synthase 2 is strongly stimulated by prostaglandins and supports G1/S-transition of saphenous vein smooth muscle cells

Hyaluronsäuresynthase 2 wird durch Prostaglandine stimuliert und fördert den G1-/S-Übergang in humanen venösen glatten Muskelzellen

Meeting Abstract

  • M. van den Boom - Universität Düsseldorf (Düsseldorf, D)
  • P. Mann - Universität Düsseldorf (Düsseldorf, D)
  • B. Levkau - Universität Düsseldorf (Düsseldorf, D)
  • K. Schrör - Universität Düsseldorf (Düsseldorf, D)
  • K. von Wnuck-Lipinski - Universität Essen (Essen, D)
  • M. Sarbia - Technische Universität München (München, D)
  • K. Grabitz - Klinik für Gefäßchirurgie und Nierentransplantation Düsseldorf (Düsseldorf, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP16

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch016.shtml

Veröffentlicht: 8. August 2006

© 2006 van den Boom et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Autologous saphenous vein bypass grafts (SVG) are frequently compromised by neointimal thickening and subsequent atherosclerosis leading to graft failure. The aim of the present study was (i) to investigate accumulation of the extracellular matrix component hyaluronic acid (HA) in native and explanted arterialized SVG, (ii) to investigate the regulation of HA-synthase (HAS) expression and (iii) to study the function of HAS2 in human saphenous vein smooth muscle cells (SMC). In native SVG and in cultured human venous SMC expression of HAS1, -2 and -3 were confirmed by semiquantitative RT-PCR and real-time RT-PCR. Vasodilatory prostaglandins (PG) strongly induced expression of HAS1, HAS2 and HA-synthesis via Gs coupled PG-receptors. Histochemistry showed a marked deposition of HA in native and arterialized vein segments in association with SMC. By small interfering RNA (siRNA) it was demonstrated that HAS2-synthesized HA is involved in SMC-proliferation. HAS2-siRNA caused a reduction of DNA-synthesis and cell number as measured by [H3]-thymidine-incorporation and growth curves. Flow cytometry showed an inhibition of cell cycle progression in the G1/S-phase. Furthermore, HAS2-siRNA downregulated cylin E and upregulated the cdk-inhibitors p21 and p27 as determined by western blotting. These data support a critical role of HAS2 in the progression of cell cycle through G1/S and proliferation. In conclusion, the present study demonstrates that HA-rich extracellular matrix is maintained after arterialization of vein grafts and may contribute to graft failure due to induction of proliferation by HA synthesis mediated by HAS2 in venous SMC