Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hofmann, NA; Barth, S; Waldeck-Weiermair, M; Klec, C; Strunk, D; Malli, R; Graier, WF.
TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation.
Biol Open. 2014; 3(12):1164-1172
Doi: 10.1242/bio.20149571
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- Führende Autor*innen der Med Uni Graz
- Graier Wolfgang
- Hofmann Nicole
- Co-Autor*innen der Med Uni Graz
- Barth Sonja
- Klec Christiane
- Malli Roland
- Strunk Dirk
- Waldeck-Weiermair Markus
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- Abstract:
- Anandamide (N-arachidonyl ethanolamide, AEA) is an endogenous cannabinoid that is involved in various pathological conditions, including cardiovascular diseases and tumor-angiogenesis. Herein, we tested the involvement of classical cannabinoid receptors (CBRs) and the Ca(2+)-channel transient receptor potential vanilloid 1 (TRPV1) on cellular AEA uptake and its effect on endothelial cell proliferation and network-formation. Uptake of the fluorescence-labeled anandamide (SKM4-45-1) was monitored in human endothelial colony-forming cells (ECFCs) and a human endothelial-vein cell line (EA.hy926). Involvement of the receptors during AEA translocation was determined by selective pharmacological inhibition (AM251, SR144528, CID16020046, SB366791) and molecular interference by TRPV1-selective siRNA-mediated knock-down and TRPV1 overexpression. We show that exclusively TRPV1 contributes essentially to AEA transport into endothelial cells in a Ca(2+)-independent manner. This TRPV1 function is a prerequisite for AEA-induced endothelial cell proliferation and network-formation. Our findings point to a so far unknown moonlighting function of TRPV1 as Ca(2+)-independent contributor/regulator of AEA uptake. We propose TRPV1 as representing a promising target for development of pharmacological therapies against AEA-triggered endothelial cell functions, including their stimulatory effect on tumor-angiogenesis. © 2014. Published by The Company of Biologists Ltd.
- Find related publications in this database (Keywords)
- transient receptor potential vanilloid 1
- TRPV1
- anandamide
- AEA
- endothelial colony-forming cells
- ECFC
- anandamide transport
- proliferation
- network-formation
- angiogenesis