Background:
Endothelial Progenitor Cells (EPCs) are important players in neovascularization,
mobilized through signalling by Angiogenic Growth Factors (AGFs) such as Vascular
Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF). In vitro, inflammatory parameters
impair the function and influence of EPCs on AGFs. However, this connection is not
clear in vivo. To understand the mechanisms of augmented arteriogenesis and angiogenesis in
acute ischemic stroke (AIS) patients, we investigated whether circulating stem cells (CD133+),
early endothelial progenitor cells (CD133+/VEGFR2+), and endothelial cells (ECs;
CD34¯/CD133¯/VEGFR2+) were increasingly mobilized during AIS, and whether there were correlations
between EPC levels, growth factor levels and inflammatory parameters.
Methods:
Data on demographics, classical vascular risk factors, neurological deficit information
(assessed using the National Institutes of Health Stroke Scale), and treatment were collected from
43 consecutive AIS patients (group I). Risk factor control patients (group II) included 22 nonstroke
subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured
by flow cytometry and the populations of circulating stem cells (CD133+), early EPCs
(CD133+/VEGFR2+), and ECs (CD34¯/CD133¯/VEGFR2+) were analysed. Correlations between
EPC levels and VEGF and FGF vascular growth factor levels as well as the influence of inflammatory
parameters on EPCs and AGFs were assessed.
Results:
Patient ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of circulating
CD34¯/CD133¯/VEGF-R2+ cells was significantly higher in AIS patients than in control
patients (p < 0.05). VEGF plasma levels were also significantly higher in AIS patients compared to
control patients on day 7 (p < 0.05). FGF plasma levels in patients with AIS were significantly
higher than those in the control group on day 3 (p < 0.05). There were no correlations between increased
VEGF and FGF levels and the number of CD133+, CD133+/VEGFR2+, or CD34¯/CD133¯/VEGFR2+ cells. Leukocyte levels, FGF plasma levels, and the number of early
EPCs were negatively correlated on day 3. High sensitivity C-reactive protein levels and the number
of CD133+ and CD133+/VEGFR2+ cells were negatively correlated on day 7. In addition,
there was a negative correlation between fibrinogen levels and FGF plasma levels as well as the
number of early EPCs (CD133+/VEGFR2+).
Conclusion:
AIS patients exhibited increased numbers of early EPCs (CD133+/VEGFR2+) and
AGF (VEGF and FGF) levels. A negative correlation between inflammatory parameters and AGFs
and EPCs indicated the unfavourable influence of inflammatory factors on EPC differentiation and
survival. Moreover, these correlations represented an important mechanism linking inflammation
to vascular disease.
Effect of β-nerve growth factor on differentiation of endothelial progenitor cells in rats
