We tested the hypothesis that
endothelial progenitor cells (EPCs) expressing vascular endothelial cell growth factor (VEGF)
receptor 1 (VEGFR1) form part of the walls of rat mesenteric microvessels. VEGF165b is a splice variant of VEGF-A that activates VEGFR1 but not VEGFR2 (Canc Res 2004 64:7822) whereas VEGF-C activates VEGFR2 but not VEGFR1 (J Vas Res 2001 38:176). Cytosolic Ca2+ concentration (
c) was imaged in the endothelial cells (ECs) in rat microvessels using Fura2-AM. Changes in c were imaged in regions of interest (ROI) of 6-10 ECs. Vessels were perfused with 1% BSA, then 1nM VEGF165b or 10nM VEGF-C and the c measured. After reperfusion with 1% BSA for 20 mins, the second VEGF was tested in the same vessel. Although VEGF165, which activates VEGFR 1& 2 significantly increases c (AJP 1997 273:H687), neither VEGF165b (baseline 88±8nM, peak 113±18nM, p>0.05, n=9 rats, paired t-test) nor VEGF-C (baseline 105±11nM, peak 150±20nM, p<0.05, n=8 rats) significantly increased the average baseline c. However, there was a heterogeneous Ca2+ response for both VEGFs. In 26% of ROIs c increased (>2SD) with VEGF165b, did not change in 72%, and decreased (>2SD) in 2% of ROIs (n=43). VEGF-C increased c in 43% of ROIs, did not change in 40% and decreased in 17% (n=35). The percent of ROI increasing c by VEGF-C was significantly greater than that by VEGF165b (p<0.01, x2 test). These results show a heterogeneous distribution of ECs in the vessels that may help to identify EPCs.