Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes

Mark S. Segal, Ronak Shah, Aqeela Afzal, Cecile M. Perrault, Kyunghee Chang, Anna Schuler, Elaine Beem, Lynn C. Shaw, Sergio Li Calzi, Jeffrey K. Harrison, Roger Tran-Son-Tay, Maria B. Grant

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Stromal-derived factor-1 (SDF-1) is a critical chemokine for endothelial progenitor cell (EPC) recruitment to areas of ischemia, allowing these cells to participate in compensatory angiogenesis. The SDF-1 receptor, CXCR4, is expressed in developing blood vessels as well as on CD34+ EPCs. We describe that picomolar and nanomolar concentrations of SDF-1 differentially influence neovascularization, inducing CD34+ cell migration and EPC tube formation. CD34+ cells isolated from diabetic patients demonstrate a marked defect in migration to SDF-1. This defect is associated, in some but not all patients, with a cell surface activity of CD26/dipeptidyl peptidase IV, an enzyme that inactivates SDF-1. Diabetic CD34+ cells also do not migrate in response to vascular endothelial growth factor and are structurally rigid. However, incubating CD34+ cells with a nitric oxide (NO) donor corrects this migration defect and corrects the cell deformability. In addition, exogenous NO alters vasodilator-stimulated phosphoprotein and mammalian-enabled distribution in EPCs. These data support a common downstream cytoskeletal alteration in diabetic CD34+ cells that is independent of growth factor receptor activation and is correctable with exogenous NO. This inability of diabetic EPCs to respond to SDF-1 may contribute to aberrant tissue vascularization and endothelial repair in diabetic patients.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalDiabetes
Volume55
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Nitric Oxide
CXCR4 Receptors
Dipeptidyl Peptidase 4
Choristoma
Growth Factor Receptors
Nitric Oxide Donors
Endothelial Progenitor Cells
Chemokines
Vascular Endothelial Growth Factor A
Cell Movement
Blood Vessels
Ischemia
Enzymes
erucylphosphocholine

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Segal, M. S., Shah, R., Afzal, A., Perrault, C. M., Chang, K., Schuler, A., ... Grant, M. B. (2006). Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes, 55(1), 102-109. https://doi.org/10.2337/diabetes.55.1.102

Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. / Segal, Mark S.; Shah, Ronak; Afzal, Aqeela; Perrault, Cecile M.; Chang, Kyunghee; Schuler, Anna; Beem, Elaine; Shaw, Lynn C.; Calzi, Sergio Li; Harrison, Jeffrey K.; Tran-Son-Tay, Roger; Grant, Maria B.

In: Diabetes, Vol. 55, No. 1, 01.2006, p. 102-109.

Research output: Contribution to journalArticle

Segal, MS, Shah, R, Afzal, A, Perrault, CM, Chang, K, Schuler, A, Beem, E, Shaw, LC, Calzi, SL, Harrison, JK, Tran-Son-Tay, R & Grant, MB 2006, 'Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes', Diabetes, vol. 55, no. 1, pp. 102-109. https://doi.org/10.2337/diabetes.55.1.102
Segal, Mark S. ; Shah, Ronak ; Afzal, Aqeela ; Perrault, Cecile M. ; Chang, Kyunghee ; Schuler, Anna ; Beem, Elaine ; Shaw, Lynn C. ; Calzi, Sergio Li ; Harrison, Jeffrey K. ; Tran-Son-Tay, Roger ; Grant, Maria B. / Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. In: Diabetes. 2006 ; Vol. 55, No. 1. pp. 102-109.
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