Journal
BIOLOGY OPEN
Volume 3, Issue 12, Pages 1164-1172Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.20149571
Keywords
transient receptor potential vanilloid 1; TRPV1; anandamide; AEA; endothelial colony-forming cells; ECFC; anandamide transport; proliferation; network-formation; angiogenesis
Categories
Funding
- Austrian Science Funds (FWF) [P20181-B05 P21857-B18, P22553-B18]
- Medical University of Graz within the Doctoral College Metabolic and Cardiovascular Disease [FWF W1226-B18]
- Austrian Science Fund (FWF) [P 22553, P 21857] Funding Source: researchfish
Ask authors/readers for more resources
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 Ca2+-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 Ca2+-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 Ca2+-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available