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Diminished MnSOD contributes to endothelial progenitor cell dysfunction, impaired angiogenesis and wound healing in type 2 diabetes
Author(s) -
Marrotte Eric J.,
Hakim Jeffrey S.,
Chen DanDan,
Chen Alex F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1200-b
Subject(s) - angiogenesis , progenitor cell , endothelial progenitor cell , oxidative stress , matrigel , endocrinology , medicine , wound healing , neovascularization , type 2 diabetes , diabetes mellitus , endothelial dysfunction , andrology , stem cell , immunology , biology , microbiology and biotechnology
Background: Circulating endothelial progenitor cells (EPCs) are both reduced and dysfunctional in diabetes with poorly understood mechanisms. Normal EPCs express intrinsically high MnSOD levels and are resistant to oxidative stress. We hypothesized that hyperglycemia‐induced oxidative stress leads to EPC dysfunction and delayed wound healing in type 2 diabetes. Method and Results: Adult male (C57BLKS/J, 10–14 weeks) type 2 diabetic db/db and their normal littermates db/+ mice (glucose 270.4±38.3 vs. 153.6±4.8 mg/dL, n=5, p<0.01) were used. EPC number was significantly lower in db/db vs. db/+ mice (n=4–5, p<0.05), paralleled by increased levels of superoxide anion (O 2 − ) (DHE positive cells, p<0.005). MnSOD mRNA and protein expressions were decreased by 50% (real time RT‐PCR, p<0.05) and 60% (Western Blot, p<0.01) in db/db vs. db/+ mice, respectively. EPC‐induced angiogenesis was impaired in db/db vs. db/+ mice (Matrigel, tubes/high powered field, p<0.05), with a concomitant delay in wound closure (32.4±2.5 vs. 15.2±0.5/days, p<0.001). EPCs (10 6 cells) of db/+ mice, when transplanted onto the wounds of db/db diabetic mice, significantly accelerated the closure rate. Conclusion: EPCs of type 2 diabetic mice have diminished MnSOD expression against oxidative stress and impaired angiogenesis. Cell therapy of EPCs from normal mice results in significant acceleration of wound repair in type 2 diabetic mice.