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Arachidonic acid-evoked Ca^{2+} signals promote nitric oxide release and proliferation in human endothelial colony forming cells

Zuccolo, E; Dragoni, S; Poletto, V; Catarsi, P; Guido, D; Rappa, A; Reforgiato, M; ... Moccia, F; + view all (2016) Arachidonic acid-evoked Ca^{2+} signals promote nitric oxide release and proliferation in human endothelial colony forming cells. Vascular Pharmacology , 87 pp. 159-171. 10.1016/j.vph.2016.09.005. Green open access

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Abstract

Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca^{2+} concentration ([Ca^{2+}]_{i}), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca^{2+} signals are mainly mediated by Transient Receptor Potential Vanilloid 4 (TRPV4) channels. Circulating endothelial colony forming cells (ECFCs) represent the only established precursors of ECs. In the present study, we, therefore, sought to elucidate whether AA promotes human ECFC (hECFC) proliferation through an increase in [Ca^{2+}]_{i} and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca^{2+}]_{i} raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca^{2+} signals required both intracellular Ca^{2+} release and external Ca^{2+} inflow. AA-induced Ca^{2+} release was mediated by inositol-1,4,5-trisphosphate receptors from the endoplasmic reticulum and by two pore channel 1 from the acidic stores of the endolysosomal system. AA-evoked Ca^{2+} entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca^{2+} entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca^{2+}]_{i} and by inhibiting eNOS activity with NG-nitro-l-arginine methyl ester (l-NAME). Finally, AA per se did not stimulate hECFC growth, but potentiated growth factors-induced hECFC proliferation in a Ca^{2+} - and NO-dependent manner. Therefore, AA-evoked Ca^{2+} signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.

Type: Article
Title: Arachidonic acid-evoked Ca^{2+} signals promote nitric oxide release and proliferation in human endothelial colony forming cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.vph.2016.09.005
Publisher version: https://doi.org/10.1016/j.vph.2016.09.005
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Endothelial colony forming cells, Arachidonic acid, Ca2+, TRPV4, Nitric oxide, Proliferation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10084501
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