File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Endothelium-selective activation of AMP-activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in mice

TitleEndothelium-selective activation of AMP-activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in mice
Authors
KeywordsAnimal experiment
Bone marrow
Carotid artery
Cell adhesion
Cell isolation
Issue Date2012
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
Citation
Circulation, 2012, v. 126 n. 10, p. 1267-1277 How to Cite?
AbstractBACKGROUND: Endothelial damage and dysfunction are crucial mediators that link diabetes mellitus with atherosclerotic cardiovascular disease. AMP-activated kinase (AMPK) has been implicated in regulation of both energy metabolism and vascular homeostasis. The present study investigated whether endothelium-selective activation of AMPK prevents diabetes mellitus-induced endothelial damage and vascular dysfunction by improving reendothelialization in mice. METHODS AND RESULTS: Transgenic mice with endothelium-selective expression of a constitutively active (CA) AMPK were generated and rendered diabetic by the injection of streptozotocin. Relaxation and reendothelialization of carotid arteries and circulating numbers of endothelial progenitor cells (EPCs) were examined after wire-induced denudation. Bone marrow-derived EPCs were isolated to monitor their in vivo and in vitro function. Compared with wild-type littermates, the CA-AMPK transgenic mice were resistant to diabetes mellitus-induced impairment in endothelium-dependent relaxation and reendothelialization of their injured carotid arteries. These changes in the transgenic mice were accompanied by increased mobilization of EPCs and enhanced incorporation of EPCs into injured blood vessels. Furthermore, EPCs from the transgenic mice exhibited augmented adhesion, migration, and tube formation capacities. At the molecular level, the expression of heme oxygenase (HO)-1 and the secretion of stromal cell-derived factor (SDF)-1alpha were upregulated in EPCs derived from the transgenic mice, whereas AMPK-mediated elevation of serum SDF-1alpha levels and improvements of EPC function and reendothelialization were all abrogated by pharmacological inhibition of heme oxygenase-1. CONCLUSIONS: Endothelium-specific AMPK activation is sufficient to protect against diabetes mellitus-induced aggravation of vascular injury by promoting EPC function and reendothelialization via upregulation of heme oxygenase-1 and SDF-1alpha.
Persistent Identifierhttp://hdl.handle.net/10722/159684
ISSN
2015 Impact Factor: 17.047
2015 SCImago Journal Rankings: 7.853
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, FYLen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorChen, Cen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2012-08-16T05:54:00Z-
dc.date.available2012-08-16T05:54:00Z-
dc.date.issued2012en_HK
dc.identifier.citationCirculation, 2012, v. 126 n. 10, p. 1267-1277en_HK
dc.identifier.issn0009-7322en_HK
dc.identifier.urihttp://hdl.handle.net/10722/159684-
dc.description.abstractBACKGROUND: Endothelial damage and dysfunction are crucial mediators that link diabetes mellitus with atherosclerotic cardiovascular disease. AMP-activated kinase (AMPK) has been implicated in regulation of both energy metabolism and vascular homeostasis. The present study investigated whether endothelium-selective activation of AMPK prevents diabetes mellitus-induced endothelial damage and vascular dysfunction by improving reendothelialization in mice. METHODS AND RESULTS: Transgenic mice with endothelium-selective expression of a constitutively active (CA) AMPK were generated and rendered diabetic by the injection of streptozotocin. Relaxation and reendothelialization of carotid arteries and circulating numbers of endothelial progenitor cells (EPCs) were examined after wire-induced denudation. Bone marrow-derived EPCs were isolated to monitor their in vivo and in vitro function. Compared with wild-type littermates, the CA-AMPK transgenic mice were resistant to diabetes mellitus-induced impairment in endothelium-dependent relaxation and reendothelialization of their injured carotid arteries. These changes in the transgenic mice were accompanied by increased mobilization of EPCs and enhanced incorporation of EPCs into injured blood vessels. Furthermore, EPCs from the transgenic mice exhibited augmented adhesion, migration, and tube formation capacities. At the molecular level, the expression of heme oxygenase (HO)-1 and the secretion of stromal cell-derived factor (SDF)-1alpha were upregulated in EPCs derived from the transgenic mice, whereas AMPK-mediated elevation of serum SDF-1alpha levels and improvements of EPC function and reendothelialization were all abrogated by pharmacological inhibition of heme oxygenase-1. CONCLUSIONS: Endothelium-specific AMPK activation is sufficient to protect against diabetes mellitus-induced aggravation of vascular injury by promoting EPC function and reendothelialization via upregulation of heme oxygenase-1 and SDF-1alpha.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.orgen_HK
dc.relation.ispartofCirculationen_HK
dc.subjectAnimal experiment-
dc.subjectBone marrow-
dc.subjectCarotid artery-
dc.subjectCell adhesion-
dc.subjectCell isolation-
dc.titleEndothelium-selective activation of AMP-activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1524-4539 (Electronic)0009-7322 (Linkin&volume=&spage=&epage=&date=2012&atitle=Endothelium-Selective+Activation+of+AMP-Activated+Protein+Kinase+Prevents+Diabetes-Induced+Impairment+in+Vascular+Function+and+Re-Endothelialization+via+Induction+of+Heme+Oxygenase-1+in+Miceen_US
dc.identifier.emailLi, FYL: francois.li@hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailChen, C: endocc@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hk-
dc.identifier.emailXu, A: amxu@hku.hk-
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/CIRCULATIONAHA.112.108159en_HK
dc.identifier.pmid22851545-
dc.identifier.scopuseid_2-s2.0-84865860473en_HK
dc.identifier.hkuros204676en_US
dc.identifier.volume126-
dc.identifier.issue10-
dc.identifier.spage1267-
dc.identifier.epage1277-
dc.identifier.eissn1524-4539-
dc.identifier.isiWOS:000308356100021-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f1000717957201-
dc.identifier.scopusauthoridXu, A=55324652300en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridWang, Y=34973738700en_HK
dc.identifier.scopusauthoridChen, C=53867897200en_HK
dc.identifier.scopusauthoridTse, HF=55325257600en_HK
dc.identifier.scopusauthoridLam, KSL=55325694500en_HK
dc.identifier.scopusauthoridLi, FYL=55232963900en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats