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 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.
McClung JA, Kruger AL, Ferraris A, Vanella L, Tsenovoy P, Weiss MB, Abraham NG. Usefulness of clopidogrel to protect against diabetes-induced vascular damage. The American Journal of Cardiology. 2010;105(7):1014-8.