Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species

Camilla F. Wenceslau, Cameron Grant Mccarthy, Theodora Szasz, R Clinton Webb

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as 'aspirin-triggered lipoxin'. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods: We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. Results: LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. Conclusion: LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin.

Original languageEnglish (US)
Pages (from-to)407-417
Number of pages11
JournalJournal of Vascular Research
Volume51
Issue number6
DOIs
StatePublished - Mar 6 2014

Fingerprint

rho-Associated Kinases
Reactive Oxygen Species
Aspirin
Lipoxins
Angioplasty
Blood Vessels
rhoA GTP-Binding Protein
Arachidonate Lipoxygenases
Coronary Restenosis
Formyl Peptide Receptor
lipoxin A4
Contractile Proteins
NADPH Oxidase
Phenylephrine
Cyclooxygenase 2
Acetylation
Acetylcholine
Endothelium
Aorta
Wistar Rats

Keywords

  • Aorta
  • Contractile responses
  • Endothelial dysfunction
  • Lipoxin A

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species. / Wenceslau, Camilla F.; Mccarthy, Cameron Grant; Szasz, Theodora; Webb, R Clinton.

In: Journal of Vascular Research, Vol. 51, No. 6, 06.03.2014, p. 407-417.

Research output: Contribution to journalArticle

Wenceslau, Camilla F. ; Mccarthy, Cameron Grant ; Szasz, Theodora ; Webb, R Clinton. / Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species. In: Journal of Vascular Research. 2014 ; Vol. 51, No. 6. pp. 407-417.
@article{7dac592db8d74fb9b171ef960de8d275,
title = "Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species",
abstract = "Background: Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as 'aspirin-triggered lipoxin'. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods: We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. Results: LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. Conclusion: LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin.",
keywords = "Aorta, Contractile responses, Endothelial dysfunction, Lipoxin A",
author = "Wenceslau, {Camilla F.} and Mccarthy, {Cameron Grant} and Theodora Szasz and Webb, {R Clinton}",
year = "2014",
month = "3",
day = "6",
doi = "10.1159/000371490",
language = "English (US)",
volume = "51",
pages = "407--417",
journal = "Journal of Vascular Research",
issn = "1018-1172",
publisher = "S. Karger AG",
number = "6",

}

TY - JOUR

T1 - Lipoxin A4 mediates aortic contraction via rhoa/rho kinase, endothelial dysfunction and reactive oxygen species

AU - Wenceslau, Camilla F.

AU - Mccarthy, Cameron Grant

AU - Szasz, Theodora

AU - Webb, R Clinton

PY - 2014/3/6

Y1 - 2014/3/6

N2 - Background: Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as 'aspirin-triggered lipoxin'. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods: We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. Results: LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. Conclusion: LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin.

AB - Background: Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as 'aspirin-triggered lipoxin'. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods: We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. Results: LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. Conclusion: LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin.

KW - Aorta

KW - Contractile responses

KW - Endothelial dysfunction

KW - Lipoxin A

UR - http://www.scopus.com/inward/record.url?scp=84924274399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924274399&partnerID=8YFLogxK

U2 - 10.1159/000371490

DO - 10.1159/000371490

M3 - Article

VL - 51

SP - 407

EP - 417

JO - Journal of Vascular Research

JF - Journal of Vascular Research

SN - 1018-1172

IS - 6

ER -