Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells

Estella Zuccolo, Silvia Dragoni, Valentina Poletto, Paolo Catarsi, Daniele Guido, Alessandra Rappa, Marta Reforgiato, Francesco Lodola, Dmitry Lim, Vittorio Rosti, Germano Guerra, Francesco Moccia

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca2+ concentration ([Ca2+]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca2+ 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 [Ca2+]i and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca2+]i raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca2+ signals required both intracellular Ca2+ release and external Ca2+ inflow. AA-induced Ca2+ 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 Ca2+ entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca2+ entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca2+]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 Ca2+- and NO-dependent manner. Therefore, AA-evoked Ca2+ signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.

Original languageEnglish
JournalVascular Pharmacology
DOIs
Publication statusAccepted/In press - Jan 29 2016

Fingerprint

Arachidonic Acid
Nitric Oxide
TRPV Cation Channels
Cell Proliferation
Inositol 1,4,5-Trisphosphate Receptors
Nitric Oxide Synthase Type III
Nitric Oxide Synthase
Endoplasmic Reticulum
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Acids
Growth

Keywords

  • Arachidonic acid
  • Ca
  • Endothelial colony forming cells
  • Nitric oxide
  • Proliferation
  • TRPV4

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells. / Zuccolo, Estella; Dragoni, Silvia; Poletto, Valentina; Catarsi, Paolo; Guido, Daniele; Rappa, Alessandra; Reforgiato, Marta; Lodola, Francesco; Lim, Dmitry; Rosti, Vittorio; Guerra, Germano; Moccia, Francesco.

In: Vascular Pharmacology, 29.01.2016.

Research output: Contribution to journalArticle

Zuccolo, Estella ; Dragoni, Silvia ; Poletto, Valentina ; Catarsi, Paolo ; Guido, Daniele ; Rappa, Alessandra ; Reforgiato, Marta ; Lodola, Francesco ; Lim, Dmitry ; Rosti, Vittorio ; Guerra, Germano ; Moccia, Francesco. / Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells. In: Vascular Pharmacology. 2016.
@article{8030fdd850534ccf833b7cd6200328a7,
title = "Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells",
abstract = "Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca2+ concentration ([Ca2+]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca2+ 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 [Ca2+]i and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca2+]i raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca2+ signals required both intracellular Ca2+ release and external Ca2+ inflow. AA-induced Ca2+ 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 Ca2+ entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca2+ entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca2+]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 Ca2+- and NO-dependent manner. Therefore, AA-evoked Ca2+ signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.",
keywords = "Arachidonic acid, Ca, Endothelial colony forming cells, Nitric oxide, Proliferation, TRPV4",
author = "Estella Zuccolo and Silvia Dragoni and Valentina Poletto and Paolo Catarsi and Daniele Guido and Alessandra Rappa and Marta Reforgiato and Francesco Lodola and Dmitry Lim and Vittorio Rosti and Germano Guerra and Francesco Moccia",
year = "2016",
month = "1",
day = "29",
doi = "10.1016/j.vph.2016.09.005",
language = "English",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells

AU - Zuccolo, Estella

AU - Dragoni, Silvia

AU - Poletto, Valentina

AU - Catarsi, Paolo

AU - Guido, Daniele

AU - Rappa, Alessandra

AU - Reforgiato, Marta

AU - Lodola, Francesco

AU - Lim, Dmitry

AU - Rosti, Vittorio

AU - Guerra, Germano

AU - Moccia, Francesco

PY - 2016/1/29

Y1 - 2016/1/29

N2 - Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca2+ concentration ([Ca2+]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca2+ 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 [Ca2+]i and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca2+]i raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca2+ signals required both intracellular Ca2+ release and external Ca2+ inflow. AA-induced Ca2+ 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 Ca2+ entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca2+ entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca2+]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 Ca2+- and NO-dependent manner. Therefore, AA-evoked Ca2+ signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.

AB - Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca2+ concentration ([Ca2+]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca2+ 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 [Ca2+]i and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca2+]i raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca2+ signals required both intracellular Ca2+ release and external Ca2+ inflow. AA-induced Ca2+ 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 Ca2+ entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca2+ entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca2+]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 Ca2+- and NO-dependent manner. Therefore, AA-evoked Ca2+ signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.

KW - Arachidonic acid

KW - Ca

KW - Endothelial colony forming cells

KW - Nitric oxide

KW - Proliferation

KW - TRPV4

UR - http://www.scopus.com/inward/record.url?scp=84994718587&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994718587&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2016.09.005

DO - 10.1016/j.vph.2016.09.005

M3 - Article

AN - SCOPUS:84994718587

JO - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

ER -