Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2
Section snippets
Materials and methods
Synthesis of AGE-modified albumin. AGE-modified albumin (AGE-albumin) was synthesized under sterile conditions by incubating 20 mg/ml bovine serum albumin (BSA, low endotoxin, Merck) with 50 mmol/L glucose for 90 days, following which the mixture was fully dialyzed against PBS to remove unbound glucose, as previously described [7]. BSA incubated without glucose under the same conditions was used as the negative control in all experiments.
EPC isolation and culture. The study followed procedures in
Characterization of EPCs
Two types of cells were observed in our culture system. One type (“early EPCs”), appeared 3–5 days after primary culture. These early EPCs were spindle shaped and appeared as clusters, but these clusters disappeared in 10–14 days. Another cell population (“late EPCs”) appeared as clusters 10–15 days after plating. Cells (20–50) with smooth cytoplasmic outlines were observed in each cluster, and each cluster gave rise to more than 500 cells, which grew to confluence and exhibited a cobblestone
Discussion
The range of AGE-albumin concentrations used in the present study (50–400 μg/ml) was chosen because it is representative of plasma concentrations of AGE-albumin found in diabetic patients, as we have previously reported [7]. Therefore, the effects of AGE-albumin observed here are likely to be replicated in diabetic patients in vivo.
Sun et al. [20] have previously reported that, when EPCs derived from peripheral BMCs are incubated with 200 μg/ml AGE-albumin for 24 h, decreased proliferation and
Acknowledgments
This project was supported by the National Science Foundation of China (Grant No. 03030201) and the Natural Science Foundation of Jiangsu Province of China (Grant No. BK2004083).
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