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

Stimulation of hyaluronic acid synthesis by bioactive lysophospholipids in human vascular smooth muscle cells

Stimulation der Hyaluronsäuresynthese durch bioaktive Lysophospholipide in humanen glatten Muskelzellen

Meeting Abstract

  • A. Marzoll - Universitätsklinikum Düsseldorf (Düsseldorf, D)
  • J.W. Fischer - Universitätsklinikum Düsseldorf (Düsseldorf, D)
  • B. Levkau - Universitätsklinikum Essen (Essen, D)
  • P. Keul - Universitätsklinikum Essen (Essen, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP17

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch017.shtml

Published: August 8, 2006

© 2006 Marzoll et al.
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Outline

Text

Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) of human atherosclerotic plaques. HA is critically involved in the fine tuning of vascular smooth muscle cell (VSMC) proliferation and migration during atherosclerosis. HA-synthase 2 (HAS2), the major HAS-isoform in VSMC is induced by a variety of factors that modulate VSMC phenotype. Bioactive lysophospholipids such as sphingosylphosphorylcholine (SPC), lysophosphatidylcholine (LPC) and sphingosine-1-phosphat (S1P) are present in high-density lipoproteins (HDL) and are responsible for part of its vasodilatory and anti-apoptotic effects. The aim of the present study was to investigate whether bioactive lysophospholipids regulate HAS2 mRNA levels in human VSMC derived from human coronary arteries. VSMC were used between passages 4-10 and were cultured under normal growth conditions. After serum deprivation for 48 h, the cells were stimulated with the respective bioactive phospholipids for 6 hours. Compared with controls, HAS2 mRNA levels were induced by SPC (5 µM) 1.8 ± 0.3 fold and by LPC (15 µM) 2.1 ± 0.6 fold. In addition, HA levels were induced by SPC (5µM) and LPC (15 µM) as detected by immunohistochemistry using HA-binding protein. S1P (1 µM) stimulated HAS2 expression 2.5 ± 0.3 fold compared to control. S1P-and SPC-induced stimulation could be reversed with Tyrphostin SU1498 (30 µM), a selective inhibitor of VEGF receptor kinase, and the effect of S1P was also abolished by Tyrphostin AG1296 (10 µM), a specific PDGF receptor kinase inhibitor. Activation of the PDGF- and VEGF-receptors by their ligands PDGF-BB (10 ng/ml) and VEGF (45 ng/ml), respectively, induced HAS2 mRNA.

In conclusion, these findings demonstrate that bioactive lysophospholipids such as S1P activate HAS2 expression and HA-synthesis in VSMC, and that this may be mediated via a transactivation of the PDGF- and VEGF-receptors