RGD Reference Report - Essential role of ICAM-1/CD18 in mediating EPC recruitment, angiogenesis, and repair to the infarcted myocardium. - Rat Genome Database

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Essential role of ICAM-1/CD18 in mediating EPC recruitment, angiogenesis, and repair to the infarcted myocardium.

Authors: Wu, Y  Ip, JE  Huang, J  Zhang, L  Matsushita, K  Liew, CC  Pratt, RE  Dzau, VJ 
Citation: Wu Y, etal., Circ Res. 2006 Aug 4;99(3):315-22. Epub 2006 Jul 6.
RGD ID: 1582375
Pubmed: PMID:16825578   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000235986.35957.a3   (Journal Full-text)

Bone marrow-derived endothelial progenitor cells (EPCs) have the ability to migrate to ischemic organs. However, the signals that mediate trafficking and recruitment of these cells are not well understood. Using a functional genomics strategy, we determined the genes that were upregulated in the ischemic myocardium and might be involved in EPC recruitment. Among them, CD18 and its ligand ICAM-1 are particularly intriguing because CD18 and its heterodimer binding chains CD11a and CD11b were correspondingly expressed in ex vivo-expanded EPCs isolated from rat and murine bone marrows. To further verify the functional role of CD18 in mediating EPC recruitment and repair to the infarcted myocardium, we used neutralizing antibody to block CD18. Blockade of CD18 in EPCs significantly inhibited their attachment capacity in vitro and reduced their recruitment to the ischemic myocardium in vivo by 95%. Moreover, mice receiving EPCs that were treated with control isotype IgG exhibited significantly increased capillary density in the infarct border zone, reduced cardiac dilatation, ventricular wall thinning, and fibrosis when compared with myocardial infarction mice receiving PBS and CD18 blockade reversed the EPC-mediated improvements to the infarcted heart. Thus, our results suggest an essential role of CD18 in mediating EPC recruitment and the subsequent functional effects on the infarcted heart.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell-cell adhesion  IMP 1582375 RGD 
endothelial cell migration  IMP 1582375 RGD 
positive regulation of angiogenesis  IMP 1582375 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface  IDA 1582375 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell adhesion molecule binding contributes_toIMP 1582375Icam1 bindingRGD 
integrin binding  IMP 1582375Itgb2/CD18 bindingRGD 

Objects Annotated

Genes (Rattus norvegicus)
Icam1  (intercellular adhesion molecule 1)
Itgb2  (integrin subunit beta 2)


Additional Information