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Targeting the endothelial progenitor cell surface proteome to identify novel mechanisms that mediate angiogenic efficacy in a rodent model of vascular disease. Physiol Genomics 2013 Nov 01;45(21):999-1011

Date

09/12/2013

Pubmed ID

24022221

Pubmed Central ID

PMC3841789

DOI

10.1152/physiolgenomics.00097.2013

Scopus ID

2-s2.0-84887110240   13 Citations

Abstract

Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials suggest autologous EPC-based therapy may be effective in treatment of vascular diseases. Albeit promising, variability in the efficacy of EPCs associated with underlying disease states has hindered the realization of EPC-based therapy. Here we first identify and characterize EPC dysfunction in a rodent model of vascular disease (SS/Mcwi rat) that exhibits impaired angiogenesis. To identify molecular candidates that mediate the angiogenic potential of these cells, we performed a broad analysis of cell surface protein expression using chemical labeling combined with mass spectrometry. Analysis revealed EPCs derived from SS/Mcwi rats express significantly more type 2 low-affinity immunoglobulin Fc-gamma (FCGR2) and natural killer 2B4 (CD244) receptors compared with controls. Genome-wide sequencing (RNA-seq) and qt-PCR confirmed isoforms of CD244 and FCGR2a transcripts were increased in SS/Mcwi EPCs. EPCs with elevated expression of FCGR2a and CD244 receptors are predicted to increase the probability of SS/Mcwi EPCs being targeted for death, providing a mechanistic explanation for their reduced angiogenic efficacy in vivo. Pathway analysis supported this contention, as "key" molecules annotated to cell death paths were differentially expressed in the SS/Mcwi EPCs. We speculate that screening and neutralization of cell surface proteins that "tag" and impair EPC function may provide an alternative approach to utilizing incompetent EPCs in greater numbers, as circulating EPCs are depleted in patients with vascular disease. Overall, novel methods to identify putative targets for repair of EPCs using discovery-based technologies will likely provide a major advance in the field of regenerative medicine.

Author List

Kaczorowski CC, Stodola TJ, Hoffmann BR, Prisco AR, Liu PY, Didier DN, Karcher JR, Liang M, Jacob HJ, Greene AS

Authors

Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD34
Cells, Cultured
Electric Stimulation
Endothelial Cells
Flow Cytometry
Humans
Mass Spectrometry
Membrane Proteins
Muscle, Skeletal
Neovascularization, Physiologic
Proteome
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Stem Cell Transplantation
Stem Cells
Transcriptome
Vascular Diseases
Vascular Endothelial Growth Factor Receptor-2
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d