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.
Wang
Yingjie
Y
Faculty of Medical Sciences, Medical School, University of Newcastle-upon-Tyne, UK.
Marshall
Sally M
SM
Thompson
Michael G
MG
Hoenich
Nicholas A
NA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D004338:Drug Combinations; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000097:blood; D018570:Risk Assessment / Q000379:methods; D012709:Serum Albumin / Q000494:pharmacology
D004338:Drug Combinations; D017127:Glycation End Products, Advanced; D010718:Phosphatidylserines; D012709:Serum Albumin