File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Lipocalin-2 deficiency prevents endothelial dysfunction associated with dietary obesity: Role of cytochrome P450 2C inhibition
  • Basic View
  • Metadata View
  • XML View
TitleLipocalin-2 deficiency prevents endothelial dysfunction associated with dietary obesity: Role of cytochrome P450 2C inhibition
 
AuthorsLiu, JTC1
Song, E1
Xu, A1 1
Berger, T2
Mak, TW2
Tse, HF1
Law, IKM1
Huang, B1
Liang, Y1
Vanhoutte, PM1
Wang, Y1
 
Keywordsadipokine
CYP2C9
endothelial dysfunction
eNOS
lipocalin-2
obesity
 
Issue Date2012
 
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
CitationBritish Journal Of Pharmacology, 2012, v. 165 n. 2, p. 520-531 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2011.01587.x
 
AbstractBackground and Purpose Lipocalin-2 is a pro-inflammatory adipokine up-regulated in obese human subjects and animal models. Its circulating levels are positively correlated with the unfavourable lipid profiles, elevated blood pressure and insulin resistance index. Augmented lipocalin-2 has been found in patients with cardiovascular abnormalities.The present study was designed to investigate the role of lipocalin-2 in regulating endothelial function and vascular reactivity. Experimental Approach Wild-type and lipocalin-2 knockout (Lcn2-KO) mice were fed with either a standard chow or a high-fat diet. Blood pressures and endothelium-dependent relaxations/contractions were monitored at 2 week intervals. Results Systolic blood pressure was elevated by high-fat diet in wild-type mice but not in Lcn2-KO mice. Endothelial dysfunction, reflected by the impaired endothelium-dependent relaxations to insulin and augmented endothelium-dependent contractions to ACh, was induced by high-fat diet in wild-type mice. In contrast, Lcn2-KO mice were largely protected from the deterioration of endothelial function caused by dietary challenges. The eNOS dimer/monomer ratio, NO bioavailability, basal and insulin-stimulated PKB/eNOS phosphorylation responses were higher in aortae of Lcn2-KO mice. Administration of lipocalin-2 attenuated endothelium-dependent relaxations to insulin and promoted endothelium-dependent contractions to ACh. It induced eNOS uncoupling and elevated COX expression in the arteries. Treatment with sulphaphenazole, a selective inhibitor of cytochrome P450 2C9, improved endothelial function in wild-type mice and blocked the effects of lipocalin-2 on both endothelium-dependent relaxations to insulin and endothelium-dependent contractions to ACh, as well as eNOS uncoupling. Conclusions Lipocalin-2, by modulating cytochrome P450 2C9 activity, is critically involved in diet-induced endothelial dysfunction. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
 
ISSN0007-1188
2012 Impact Factor: 5.067
2012 SCImago Journal Rankings: 1.488
 
DOIhttp://dx.doi.org/10.1111/j.1476-5381.2011.01587.x
 
PubMed Central IDPMC3268203
 
ISI Accession Number IDWOS:000298481200018
Funding AgencyGrant Number
University of Hong Kong
Hong Kong Research Grant CouncilHKU777908M
HKU777208M
HKU780410M
Collaborative Research FundHKU2/07C
4/HKU/10C
Funding Information:

This work was supported by the grants from Seeding Funds for Basic Research of the University of Hong Kong; Hong Kong Research Grant Council grants (HKU777908M, HKU777208M and HKU780410M) and Collaborative Research Fund (HKU2/07C and 4/HKU/10C).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, JTC
 
dc.contributor.authorSong, E
 
dc.contributor.authorXu, A
 
dc.contributor.authorBerger, T
 
dc.contributor.authorMak, TW
 
dc.contributor.authorTse, HF
 
dc.contributor.authorLaw, IKM
 
dc.contributor.authorHuang, B
 
dc.contributor.authorLiang, Y
 
dc.contributor.authorVanhoutte, PM
 
dc.contributor.authorWang, Y
 
dc.date.accessioned2011-07-27T01:30:26Z
 
dc.date.available2011-07-27T01:30:26Z
 
dc.date.issued2012
 
dc.description.abstractBackground and Purpose Lipocalin-2 is a pro-inflammatory adipokine up-regulated in obese human subjects and animal models. Its circulating levels are positively correlated with the unfavourable lipid profiles, elevated blood pressure and insulin resistance index. Augmented lipocalin-2 has been found in patients with cardiovascular abnormalities.The present study was designed to investigate the role of lipocalin-2 in regulating endothelial function and vascular reactivity. Experimental Approach Wild-type and lipocalin-2 knockout (Lcn2-KO) mice were fed with either a standard chow or a high-fat diet. Blood pressures and endothelium-dependent relaxations/contractions were monitored at 2 week intervals. Results Systolic blood pressure was elevated by high-fat diet in wild-type mice but not in Lcn2-KO mice. Endothelial dysfunction, reflected by the impaired endothelium-dependent relaxations to insulin and augmented endothelium-dependent contractions to ACh, was induced by high-fat diet in wild-type mice. In contrast, Lcn2-KO mice were largely protected from the deterioration of endothelial function caused by dietary challenges. The eNOS dimer/monomer ratio, NO bioavailability, basal and insulin-stimulated PKB/eNOS phosphorylation responses were higher in aortae of Lcn2-KO mice. Administration of lipocalin-2 attenuated endothelium-dependent relaxations to insulin and promoted endothelium-dependent contractions to ACh. It induced eNOS uncoupling and elevated COX expression in the arteries. Treatment with sulphaphenazole, a selective inhibitor of cytochrome P450 2C9, improved endothelial function in wild-type mice and blocked the effects of lipocalin-2 on both endothelium-dependent relaxations to insulin and endothelium-dependent contractions to ACh, as well as eNOS uncoupling. Conclusions Lipocalin-2, by modulating cytochrome P450 2C9 activity, is critically involved in diet-induced endothelial dysfunction. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationBritish Journal Of Pharmacology, 2012, v. 165 n. 2, p. 520-531 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1476-5381.2011.01587.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1476-5381.2011.01587.x
 
dc.identifier.epage531
 
dc.identifier.hkuros187316
 
dc.identifier.hkuros195686
 
dc.identifier.isiWOS:000298481200018
Funding AgencyGrant Number
University of Hong Kong
Hong Kong Research Grant CouncilHKU777908M
HKU777208M
HKU780410M
Collaborative Research FundHKU2/07C
4/HKU/10C
Funding Information:

This work was supported by the grants from Seeding Funds for Basic Research of the University of Hong Kong; Hong Kong Research Grant Council grants (HKU777908M, HKU777208M and HKU780410M) and Collaborative Research Fund (HKU2/07C and 4/HKU/10C).

 
dc.identifier.issn0007-1188
2012 Impact Factor: 5.067
2012 SCImago Journal Rankings: 1.488
 
dc.identifier.issue2
 
dc.identifier.pmcidPMC3268203
 
dc.identifier.pmid21740414
 
dc.identifier.scopuseid_2-s2.0-83755172751
 
dc.identifier.spage520
 
dc.identifier.urihttp://hdl.handle.net/10722/135237
 
dc.identifier.volume165
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBritish Journal of Pharmacology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.
 
dc.subject.meshAorta, Thoracic - drug effects - metabolism - physiopathology
 
dc.subject.meshEndothelium, Vascular - drug effects - physiopathology
 
dc.subject.meshLipocalins - genetics - physiology
 
dc.subject.meshObesity - metabolism - physiopathology
 
dc.subject.meshOncogene Proteins - deficiency - genetics - physiology
 
dc.subjectadipokine
 
dc.subjectCYP2C9
 
dc.subjectendothelial dysfunction
 
dc.subjecteNOS
 
dc.subjectlipocalin-2
 
dc.subjectobesity
 
dc.titleLipocalin-2 deficiency prevents endothelial dysfunction associated with dietary obesity: Role of cytochrome P450 2C inhibition
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Liu, JTC</contributor.author>
<contributor.author>Song, E</contributor.author>
<contributor.author>Xu, A</contributor.author>
<contributor.author>Berger, T</contributor.author>
<contributor.author>Mak, TW</contributor.author>
<contributor.author>Tse, HF</contributor.author>
<contributor.author>Law, IKM</contributor.author>
<contributor.author>Huang, B</contributor.author>
<contributor.author>Liang, Y</contributor.author>
<contributor.author>Vanhoutte, PM</contributor.author>
<contributor.author>Wang, Y</contributor.author>
<date.accessioned>2011-07-27T01:30:26Z</date.accessioned>
<date.available>2011-07-27T01:30:26Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>British Journal Of Pharmacology, 2012, v. 165 n. 2, p. 520-531</identifier.citation>
<identifier.issn>0007-1188</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/135237</identifier.uri>
<description.abstract>Background and Purpose Lipocalin-2 is a pro-inflammatory adipokine up-regulated in obese human subjects and animal models. Its circulating levels are positively correlated with the unfavourable lipid profiles, elevated blood pressure and insulin resistance index. Augmented lipocalin-2 has been found in patients with cardiovascular abnormalities.The present study was designed to investigate the role of lipocalin-2 in regulating endothelial function and vascular reactivity. Experimental Approach Wild-type and lipocalin-2 knockout (Lcn2-KO) mice were fed with either a standard chow or a high-fat diet. Blood pressures and endothelium-dependent relaxations/contractions were monitored at 2 week intervals. Results Systolic blood pressure was elevated by high-fat diet in wild-type mice but not in Lcn2-KO mice. Endothelial dysfunction, reflected by the impaired endothelium-dependent relaxations to insulin and augmented endothelium-dependent contractions to ACh, was induced by high-fat diet in wild-type mice. In contrast, Lcn2-KO mice were largely protected from the deterioration of endothelial function caused by dietary challenges. The eNOS dimer/monomer ratio, NO bioavailability, basal and insulin-stimulated PKB/eNOS phosphorylation responses were higher in aortae of Lcn2-KO mice. Administration of lipocalin-2 attenuated endothelium-dependent relaxations to insulin and promoted endothelium-dependent contractions to ACh. It induced eNOS uncoupling and elevated COX expression in the arteries. Treatment with sulphaphenazole, a selective inhibitor of cytochrome P450 2C9, improved endothelial function in wild-type mice and blocked the effects of lipocalin-2 on both endothelium-dependent relaxations to insulin and endothelium-dependent contractions to ACh, as well as eNOS uncoupling. Conclusions Lipocalin-2, by modulating cytochrome P450 2C9 activity, is critically involved in diet-induced endothelial dysfunction. &#169; 2011 The Authors. British Journal of Pharmacology &#169; 2011 The British Pharmacological Society.</description.abstract>
<language>eng</language>
<publisher>John Wiley &amp; Sons Ltd. The Journal&apos;s web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&amp;site=1</publisher>
<relation.ispartof>British Journal of Pharmacology</relation.ispartof>
<rights>British Journal of Pharmacology. Copyright &#169; John Wiley &amp; Sons Ltd.</rights>
<subject>adipokine</subject>
<subject>CYP2C9</subject>
<subject>endothelial dysfunction</subject>
<subject>eNOS</subject>
<subject>lipocalin-2</subject>
<subject>obesity</subject>
<subject.mesh>Aorta, Thoracic - drug effects - metabolism - physiopathology</subject.mesh>
<subject.mesh>Endothelium, Vascular - drug effects - physiopathology</subject.mesh>
<subject.mesh>Lipocalins - genetics - physiology</subject.mesh>
<subject.mesh>Obesity - metabolism - physiopathology</subject.mesh>
<subject.mesh>Oncogene Proteins - deficiency - genetics - physiology</subject.mesh>
<title>Lipocalin-2 deficiency prevents endothelial dysfunction associated with dietary obesity: Role of cytochrome P450 2C inhibition</title>
<type>Article</type>
<description.nature>link_to_OA_fulltext</description.nature>
<identifier.doi>10.1111/j.1476-5381.2011.01587.x</identifier.doi>
<identifier.pmid>21740414</identifier.pmid>
<identifier.pmcid>PMC3268203</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-83755172751</identifier.scopus>
<identifier.hkuros>187316</identifier.hkuros>
<identifier.hkuros>195686</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-83755172751&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>165</identifier.volume>
<identifier.issue>2</identifier.issue>
<identifier.spage>520</identifier.spage>
<identifier.epage>531</identifier.epage>
<identifier.isi>WOS:000298481200018</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
<bitstream.url>http://hub.hku.hk/bitstream/10722/135237/1/re01.htm</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Ontario Cancer Institute University of Toronto