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Thromboxane-Dependent CD40 Ligand Release in Type 2 Diabetes Mellitus

Francesca Santilli, MD^_*, Giovanni Davì, MD^_*,_*, Agostino Consoli, MD^_*, Francesco Cipollone, MD^_*, Andrea Mezzetti, MD^_*, Angela Falco, MD^_*, Tea Taraborelli, PhD^_*, Eleonora Devangelio, MD^_*, Giovanni Ciabattoni, MD^_*, Stefania Basili, MD and Carlo Patrono, MD

^_* Center of Excellence on Aging and Departments of Medicine and Drug Sciences, University of Chieti G. D’Annunzio Schools of Medicine and Pharmacy, Chieti, Italy
Department of Medical Therapy, University of Rome La Sapienza, Rome, Italy.
Department of Pharmacology, University of Rome La Sapienza, Rome, Italy.

View larger version (21K): [in a new window]   Figure 1 Box and whisker plots of urinary excretion of 11-dehydro-thromboxane (TX)B2 (A), 8-iso-prostaglandin F2 (B), and plasma levels of CD40L (C) in healthy patients and in type 2 diabetic patients. PG = prostaglandin.

View larger version (20K): [in a new window]   Figure 2 Correlation between 8-iso-PGF2 and 11-dehydro-TXB2 excretion rates in type 2 diabetic patients according to quartiles of plasma CD40L. Vertical and horizontal lines mark the boundaries of median values of both urinary metabolites. Open and closed circles represent individual measurements, according to plasma CD40L: open circles = first and second quartile; solid circles = third and fourth quartile. PG = prostaglandin; TX = thromboxane.

View larger version (31K): [in a new window]   Figure 3 Urinary excretion rates of 8-iso-prostaglandin F2 (A), 11-dehydro-TXB2 (B), and plasma levels of CD40L (C) in 20 type 2 diabetic patients before and after improved metabolic control. Both individual measurements and box and whisker plots are shown. PG = prostaglandin; TX = thromboxane.

View larger version (18K): [in a new window]   Figure 4 Time course of plasma CD40 levels before (time 0), during 7 days of aspirin treatment (30, 100, and 325 mg/day, respectively), and at 3, 7, and 10 days after aspirin withdrawal in 18 type 2 diabetic patients. Mean ± 1 standard deviation values are shown (n = 6). *p < 0.003 vs. baseline.

View larger version (13K): [in a new window]   Figure 5 Time course of plasma CD40 levels before (time 0), during 7 days of aspirin treatment (100 mg/day), and at 3, 7, and 10 days after aspirin withdrawal in 6 healthy volunteers. Mean ± 1 standard deviation values are shown (n = 6). *p < 0.004 vs. baseline.

View larger version (25K): [in a new window]   Figure 6 Role of CD40L in the biochemical mechanisms linking hyperglycemia, inflammation, lipid peroxidation, and platelet activation. Potential amplification loops sustaining this chain of events are also shown. PG = prostaglandin; sCD40L = soluble CD40 ligand; TX = thromboxane.