Usefulness of Clopidogrel to Protect Against Diabetes-Induced Vascular Damage

• Published in: The American journal of cardiology 2010-04, Vol.105 (7), p.1014-1018
• Main Authors: McClung, John A., MD, Kruger, Adam L., DO, Ferraris, Ambra, MD, Vanella, Luca, PhD, Tsenovoy, Petr, MD, Weiss, Melvin B., MD, Abraham, Nader G., PhD
• Format: Article
• Language: English
• Subjects: Adenosine; Adult; Aged; Biological and medical sciences; Blood vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Cell Count; Cells; Diabetes; Diabetes Complications - prevention & control; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Drugs; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - drug effects; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Kinases; Male; Medical sciences; Microscopy; Middle Aged; Platelet Aggregation Inhibitors - therapeutic use; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Vascular Diseases - etiology; Vascular Diseases - prevention & control
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2009.11.034

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