Cardiovascular risk in patients with end-stage renal disease: a potential role for advanced glycation end products

Cardiovascular complications are a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Advanced glycation end products (AGE) are elevated in the plasma of such patients and are also found in atherosclerotic plaques. The cellular signalling pathway(s) underlying AGE-induced platelet aggregation have not been elucidated. One pathway currently receiving increased attention is the externalization of the membrane phospholipid, phosphatidylserine (PS), which plays an important role in the activation of clotting factors. In this study, we have investigated ex vivo a possible link between elevated AGE concentration and PS externalization. We observed (i) increased PS externalization in platelets from patients with ESRD, (ii) reconstitution of healthy platelets with serum from patients with ESRD resulted in increased PS externalization and (iii) incubation of platelets with purified human serum albumin (HSA)-AGE elicited PS externalization suggesting a role for AGE.