TY - JOUR
T1 - Adenosine A2A receptor activation promotes wound neovascularization by stimulating angiogenesis and vasculogenesis
AU - Montesinos, M. Carmen
AU - Shaw, Jason P.
AU - Yee, Herman
AU - Shamamian, Peter
AU - Cronstein, Bruce N.
N1 - Funding Information:
Supported by National Institutes of Health grants AR41911 and GM56268 , King Pharmaceuticals, Inc., the General Clinical Research Center ( M01RR00096 ), the Kaplan Comprehensive Cancer Center (to B.N.C.), the Dr. Leo Shifrin and Roslyn Myers Foundation, Breast Cancer Discovery Research Fund (to P.S.) and the Ignatz and Catherine Mayer Surgical Oncology Research Fellowship (to J.P.S.).
PY - 2004/6
Y1 - 2004/6
N2 - Recent reports indicate that circulating endothelial progenitor cells (EPCs) may be recruited to sites of neovascularization where they differentiate into endothelial cells (EC). As we have previously demonstrated that adenosine A2A agonists promote neovascularization in wounds, we sought to determine whether adenosine A2A receptor agonist-augmented wound healing involves vessel sprouting (angiogenesis) or EPC recruitment (vasculogenesis) or both. Four weeks after bone marrow reconstitution from donor FVB/N Tie2GFP transgenic mice, two full-thickness excisional wounds were performed on the dorsum of FVB/N wild-type mice and treated with either an A2A receptor agonist (CGS-21680) or vehicle alone. Vessel density, as measured by CD31 staining, and density of EPC-derived vessels, as measured by GFP expression, were quantified in a blinded fashion using two-color fluorescence microscopy. We observed nearly a three-fold increase in CD31-positive vessels and a more than 10-fold increase in GFP-positive cells in A2A agonist-treated 3-day old wounds, but by 6 days after wounding the differences between A2A agonist-treated and vehicle-treated wounds were no longer statistically significant. In conclusion, this is the first evidence that an exogenous agent such as an adenosine A2A receptor agonist increases neovascularization in the early stages of wound repair by increasing both EPC recruitment (vasculogenesis) and local vessel sprouting (angiogenesis).
AB - Recent reports indicate that circulating endothelial progenitor cells (EPCs) may be recruited to sites of neovascularization where they differentiate into endothelial cells (EC). As we have previously demonstrated that adenosine A2A agonists promote neovascularization in wounds, we sought to determine whether adenosine A2A receptor agonist-augmented wound healing involves vessel sprouting (angiogenesis) or EPC recruitment (vasculogenesis) or both. Four weeks after bone marrow reconstitution from donor FVB/N Tie2GFP transgenic mice, two full-thickness excisional wounds were performed on the dorsum of FVB/N wild-type mice and treated with either an A2A receptor agonist (CGS-21680) or vehicle alone. Vessel density, as measured by CD31 staining, and density of EPC-derived vessels, as measured by GFP expression, were quantified in a blinded fashion using two-color fluorescence microscopy. We observed nearly a three-fold increase in CD31-positive vessels and a more than 10-fold increase in GFP-positive cells in A2A agonist-treated 3-day old wounds, but by 6 days after wounding the differences between A2A agonist-treated and vehicle-treated wounds were no longer statistically significant. In conclusion, this is the first evidence that an exogenous agent such as an adenosine A2A receptor agonist increases neovascularization in the early stages of wound repair by increasing both EPC recruitment (vasculogenesis) and local vessel sprouting (angiogenesis).
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U2 - 10.1016/S0002-9440(10)63749-2
DO - 10.1016/S0002-9440(10)63749-2
M3 - Article
C2 - 15161625
AN - SCOPUS:2442689337
SN - 0002-9440
VL - 164
SP - 1887
EP - 1892
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -