Usefulness of Clopidogrel to Protect Against Diabetes-Induced Vascular Damage
Clopidogrel enhances the levels of endothelial nitric oxide and prostacyclin in tissue culture. We have previously described a marked increase in circulating endothelial cells (CECs), an ex vivo indicator of vascular injury, in patients with type 2 diabetes mellitus. We hypothesized that clopidogrel...
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Published in | The American journal of cardiology Vol. 105; no. 7; pp. 1014 - 1018 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Inc
01.04.2010
Elsevier Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Clopidogrel enhances the levels of endothelial nitric oxide and prostacyclin in tissue culture. We have previously described a marked increase in circulating endothelial cells (CECs), an ex vivo indicator of vascular injury, in patients with type 2 diabetes mellitus. We hypothesized that clopidogrel treatment would result in a decrease in CEC number and increased activity of endothelial progenitor cell recruitment signaling pathways in diabetic patients. CECs were isolated from the peripheral blood of 9 patients with type 2 diabetes using anti-CD146-coated Dynabeads. The cells were stained with acridine orange and counted by fluorescence microscopy. Endothelial progenitor cells were isolated in a similar fashion using anti-CD34 and anti-CD133 and assayed for expression of phosphorylated Akt and phosphorylated adenosine monophosphate kinase. The patients were then treated with clopidogrel 75 mg/day for 30 days, after which repeat blood specimens were analyzed. As previously observed, diabetic patients had an elevated number of CECs (mean 79 ± 15 cells/ml peripheral blood), which was reduced by clopidogrel treatment (mean 10 ± 4 cells/ml; p <0.001). This was associated with a significant increase in the expression of both phosphorylated Akt and phosphorylated adenosine monophosphate kinase (p ≤0.05). In conclusion, clopidogrel reduces endothelial cell sloughing and increases expression of endothelial progenitor cell phosphorylated Akt and phosphorylated adenosine monophosphate kinase in the peripheral blood of patients with type 2 diabetes mellitus. This represents a novel mechanism by which this agent can promote improved vascular function, protect against oxidative stress, inhibit apoptosis, and attenuate vascular damage in patients with diabetes mellitus. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0002-9149 1879-1913 |
DOI: | 10.1016/j.amjcard.2009.11.034 |