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Article: Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway

TitleAdiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway
Authors
Issue Date2010
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2010, v. 59 n. 11, p. 2949-2959 How to Cite?
AbstractOBJECTIVE - A reduced number of circulating endothelial progenitor cells (EPCs) are casually associated with the cardiovascular complication of diabetes. Adiponectin exerts multiple protective effects against cardiovascular disease, independent of its insulin-sensitizing activity. The objective of this study was to investigate whether adiponectin plays a role in modulating the bioavailability of circulating EPCs and endothelial repair. RESEARCH DESIGN AND METHODS - Adiponectin knockout mice were crossed with db+/- mice to produce db/db diabetic mice without adiponectin. Circulating number of EPCs were analyzed by flow cytometry. Reendothelialization was evaluated by staining with Evans blue after wire-induced carotid injury. RESULTS - In adiponectin knockout mice, the number of circulating EPCs decreased in an age-dependent manner compared with the wild-type controls, and this difference was reversed by the chronic infusion of recombinant adiponectin. In db/db diabetic mice, the lack of adiponectin aggravated the hyperglycemia-induced decrease in circulating EPCs and also diminished the stimulatory effects of the PPARγ agonist rosiglitazone on EPC production and reendothelialization. In EPCs isolated from both human peripheral blood and mouse bone marrow, treatment with adiponectin prevented high glucose-induced premature senescence. At the molecular level, adiponectin decreased high glucose-induced accumulation of intracellular reactive oxygen species and consequently suppressed activation of p38 MAP kinase (MAPK) and expression of the senescence marker p16INK4A. CONCLUSIONS - Adiponectin prevents EPC senescence by inhibiting the ROS/p38 MAPK/p16 INK4A signaling cascade. The protective effects of adiponectin against diabetes vascular complications are attributed in part to its ability to counteract hyperglycemia-mediated decrease in the number of circulating EPCs. © 2010 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/142385
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 2/07C
HKU 779707M
National Basic Research Program of China2011CB504004
National Natural Science Foundation of China30771024
Funding Information:

This work was supported by collaborative research fund HKU 2/07C and general research fund HKU 779707M from the Research Grants Council of Hong Kong and by the National Basic Research Program of China (2011CB504004). Y.L. was supported by the National Natural Science Foundation of China (30771024).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChang, Jen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorHoo, RLCen_HK
dc.contributor.authorWong, WTen_HK
dc.contributor.authorCheng, KKYen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2011-10-28T02:44:51Z-
dc.date.available2011-10-28T02:44:51Z-
dc.date.issued2010en_HK
dc.identifier.citationDiabetes, 2010, v. 59 n. 11, p. 2949-2959en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142385-
dc.description.abstractOBJECTIVE - A reduced number of circulating endothelial progenitor cells (EPCs) are casually associated with the cardiovascular complication of diabetes. Adiponectin exerts multiple protective effects against cardiovascular disease, independent of its insulin-sensitizing activity. The objective of this study was to investigate whether adiponectin plays a role in modulating the bioavailability of circulating EPCs and endothelial repair. RESEARCH DESIGN AND METHODS - Adiponectin knockout mice were crossed with db+/- mice to produce db/db diabetic mice without adiponectin. Circulating number of EPCs were analyzed by flow cytometry. Reendothelialization was evaluated by staining with Evans blue after wire-induced carotid injury. RESULTS - In adiponectin knockout mice, the number of circulating EPCs decreased in an age-dependent manner compared with the wild-type controls, and this difference was reversed by the chronic infusion of recombinant adiponectin. In db/db diabetic mice, the lack of adiponectin aggravated the hyperglycemia-induced decrease in circulating EPCs and also diminished the stimulatory effects of the PPARγ agonist rosiglitazone on EPC production and reendothelialization. In EPCs isolated from both human peripheral blood and mouse bone marrow, treatment with adiponectin prevented high glucose-induced premature senescence. At the molecular level, adiponectin decreased high glucose-induced accumulation of intracellular reactive oxygen species and consequently suppressed activation of p38 MAP kinase (MAPK) and expression of the senescence marker p16INK4A. CONCLUSIONS - Adiponectin prevents EPC senescence by inhibiting the ROS/p38 MAPK/p16 INK4A signaling cascade. The protective effects of adiponectin against diabetes vascular complications are attributed in part to its ability to counteract hyperglycemia-mediated decrease in the number of circulating EPCs. © 2010 by the American Diabetes Association.en_HK
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subject.meshAdiponectin - deficiency - therapeutic use-
dc.subject.meshAging-
dc.subject.meshCell Aging - drug effects - physiology-
dc.subject.meshEndothelial Cells - drug effects - metabolism - physiology-
dc.subject.meshStem Cells - drug effects - metabolism - physiology-
dc.titleAdiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=59&issue=11&spage=2949&epage=2959&date=2010&atitle=Adiponectin+prevents+diabetic+premature+senescence+of+endothelial+progenitor+cells+and+promotes+endothelial+repair+by+suppressing+the+p38+MAP+kinase/p16INK4A+signaling+pathwayen_US
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hken_HK
dc.identifier.emailCheng, KKY: dorncky@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityHoo, RLC=rp01334en_HK
dc.identifier.authorityCheng, KKY=rp01672en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.2337/db10-0582en_HK
dc.identifier.pmid20802255-
dc.identifier.pmcidPMC2963556-
dc.identifier.scopuseid_2-s2.0-78049279362en_HK
dc.identifier.hkuros184657en_US
dc.identifier.hkuros226356-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78049279362&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2949en_HK
dc.identifier.epage2959en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000284133400034-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.relation.projectAPPL1 as a novel modulator of endothelial nitric oxide production and endothelium-dependent vasodilation-
dc.identifier.scopusauthoridChang, J=36652440000en_HK
dc.identifier.scopusauthoridLi, Y=35210753800en_HK
dc.identifier.scopusauthoridHuang, Y=7501573013en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridHoo, RLC=6602369766en_HK
dc.identifier.scopusauthoridWong, WT=35932584500en_HK
dc.identifier.scopusauthoridCheng, KKY=7402997599en_HK
dc.identifier.scopusauthoridWang, Y=36653456700en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

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