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- FITC, fluorescein isothiocyanate
- PBS, phosphate-buffered saline
- PE, phycoerythrin
- RANTES, regulated on activation normal T cell expressed presumed secreted
- sCD40L, soluble CD40 ligand
Patients with diabetes mellitus have an increased risk of developing atherosclerosis and its sequelae. Atherosclerosis is an inflammatory disease involving multiple interactions between platelets, leucocytes and endothelial cells.1 Clopidogrel, a specific antagonist of the ADP P2Y12 receptor, inhibits both platelet activation and aggregation induced by ADP.2 Although clopidogrel has well-documented antithrombotic actions, its potential anti-inflammatory effects have been little investigated. We examined whether specific platelet inhibition with clopidogrel would reduce systemic inflammatory markers and specifically platelet, monocyte and endothelial activation in patients with type 2 diabetes mellitus.
We enrolled 20 patients with type 2 diabetes mellitus without clinical evidence of cardiovascular disease, malignancy, chronic inflammatory disorders, intercurrent illness, renal or hepatic insufficiency or contraindications to clopidogrel who had not taken antiplatelet agents within the preceding two weeks. Ethical approval was obtained from the local ethics committee and all participants provided written informed consent. They were treated with clopidogrel 75 mg daily for 28 days. Fasting peripheral venous blood samples were obtained at baseline and at 28 days.
Plasma concentrations of soluble CD40 ligand (sCD40L) (Bender MedSystems) and sE-selectin (R&D Systems) were determined by enzyme-linked immunosorbent assays. Plasma concentrations of the chemokine regulated on activation normal T cell expressed presumed secreted (RANTES, CCL5) were assessed with the human chemokine flow cytometric bead array (BD Biosciences).
To evaluate …
Grant support: Drs Harding and Din were supported by grants from the British Heart Foundation (PG/2001/068; PG/03/009)
Competing interests: Professor Fox has received grant support for the Global Registry of Acute Coronary Events (GRACE) from Sanofi-Aventis. All other authors have no conflict of interest to declare