Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells

Ashay D. Bhatwadekar, Josephine V. Glenn, Tim M. Curtis, Maria B. Grant, Alan W. Stitt, Tom A. Gardiner

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

PURPOSE. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. METHODS. Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. RESULTS. Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05- 0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-α when compared to control medium; SDF-1 remained unchanged. CONCLUSIONS. The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment.

Original languageEnglish (US)
Pages (from-to)4967-4973
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number10
DOIs
StatePublished - Dec 1 2009

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Endothelial Cells
Apoptosis
E-Selectin
Vascular Endothelium
Wounds and Injuries
Conditioned Culture Medium
Interleukin-8
Chemokines
Vascular Endothelial Growth Factor A
Blood Vessels
Endothelial Progenitor Cells
Extracellular Vesicles
Interleukin-6
Cell Death
Bone Marrow
Cytokines
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. / Bhatwadekar, Ashay D.; Glenn, Josephine V.; Curtis, Tim M.; Grant, Maria B.; Stitt, Alan W.; Gardiner, Tom A.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 10, 01.12.2009, p. 4967-4973.

Research output: Contribution to journalArticle

Bhatwadekar, Ashay D. ; Glenn, Josephine V. ; Curtis, Tim M. ; Grant, Maria B. ; Stitt, Alan W. ; Gardiner, Tom A. / Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 10. pp. 4967-4973.
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N2 - PURPOSE. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. METHODS. Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. RESULTS. Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05- 0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-α when compared to control medium; SDF-1 remained unchanged. CONCLUSIONS. The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment.

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