gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Expression and functional study of ccm1, ccm2 and ccm3 genes in endothelial cells of cerebral cavernous malformations (CCMs)

Untersuchung der Expression und Funktion des ccm1, ccm2 and ccm3 Gens in Endothelzellen zerebraler Kavernome

Meeting Abstract

  • corresponding author Y. Zhu - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • M. Fass - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • B. Hansen - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • Q. Wu - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • H. Bertalanffy - Neurochirurgische Klinik, Universitätsspital Zürich
  • U. Sure - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 058

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc327.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Zhu 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

Objective: CCMs affect around 0.5% populations and present as recurrent headaches, seizures and hemorrhagic stroke. The mutation of ccm1, ccm2 and ccm3 genes has been frequently reported in familial CCMs. However, the expression profile, and particularly the functions of these genes remain largely unknown. The present work aimed to study the expression of ccm1, cccm2 and ccm3 genes in purified endothelial cells (ECs) from CCMs, and furthermore, to explore the potential functions of these genes.

Methods: ECs were isolated, purified and cultured from the fresh surgical specimens of CCMs (CCM-ECs) and epilepsies (Epi-ECs, as controls). The expression of ccm1, ccm2 and ccm3 genes was detected by real-time PCR. The response of these two types of ECs to apoptotic stimuli was compared after exposure to 50 nM staurosporine (STS), a well accepted apoptosis inducer. The proliferation profile of ECs was checked after ccm1 gene silencing using siRNA technique.

Results: Real-time PCR revealed a 2-fold lower level of ccm1 gene in CCM-ECs in comparison to the Epi-ECs (p<0.05), whereas ccm2 gene was similarly expressed in CCM-ECS and in Epi-ECs. Interestingly, around 3-fold higher expression of ccm3 genes was detected in CCM-ECs than that of Epi-ECs. Of note, CCM-ECs appeared more resistant to apoptotic damage induced by STS compared with Epi-ECs (p<0.001), which may be associated with the higher expression of ccm3 in CCM-ECs. Furthermore, ccm1 gene silencing resulted in a significant reduction of endothelial proliferation (p<0.001).

Conclusions: We reported here for the first time a distinct expression pattern of ccm1, ccm2 and ccm3 genes in pure ECs of CCMs. Ccm1 gene seems to be involved in the regulation of EC proliferation, whereas ccm3 gene likely plays a critical role in anti-apoptosis. These findings may advance our understanding of these genes and support the notion that impaired expression of these genes may potentially contribute to the pathogenesis of CCM.