Decreased plasma soluble rage in patients with hypercholesterolemia: effects of statins
Abstract number: OC-TU-088
Vazzana1 N., Santilli1 F., Bucciarelli2 L.G., Noto3 D., Cefalů3 A.B., Davě3 V., Ferrante1 E., Pettinella1 C., Averna3 M., Ciabattoni4 G., Davě1 G.
11Department of Medicine, University of Chieti School of Medicine, Chieti 22Department of Medicine, Istituto Clinico Humanitas IRCCS, Rozzano, Milan 33Department of Internal Medicine, Faculty of Medicine, University of Palermo, Palermo 44Department of Drug Sciences, University of Chieti School of Pharmacy, Chieti, Italy
How-to-cite Vazzana N, Santilli F, Bucciarelli LG, Noto D, Cefalů AB, Davě V, Ferrante E, Pettinella C, Averna M, Ciabattoni G, Davě G. Decreased plasma soluble rage in patients with hypercholesterolemia: effects of statins. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract OC-TU-088
Background: The ligand – receptor for advanced glycation end products (RAGE) axis has emerged as a novel pathway involved in atherosclerosis initiation and progression. A soluble RAGE isoform (sRAGE) neutralizes the ligand-mediated damage by acting as a decoy. In hypercholesterolemia, up-regulation of the ligand – RAGE axis may bridge oxidative stress with endothelial dysfunction.
Methods: We measured in 60 hypercholesterolemic patients and 20 controls plasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) F2α excretion, and plasma levels of asymmetric dimethylarginine (ADMA). The effects of two structurally different statins (pravastatin and atorvastatin) on these parameters were analyzed in 20 hypercholesterolemic subjects free of vascular disease.
Results: Plasma sRAGE was significantly lower, ADMA and urinary 8-iso-PGF2α were significantly higher in hypercholesterolemic versus control subjects. Interestingly, patients with a previous myocardial infarction on chronic statin treatment showed plasma sRAGE levels and urinary excretion of 8-iso-PGF2α respectively higher and lower than untreated patients without cardiovascular events. On multivariate regression analysis, 8-iso-PGF2α and ADMA independently predicted sRAGE levels. An 8-week treatment with either statin was associated with a significant reduction in urinary 8-iso-PGF2α, whereas only atorvastatin raised sRAGE levels near to normal values, with no change in ADMA levels.
Conclusions: sRAGE might represent an endogenous protection factor against the occurrence of accelerated atherosclerosis mediated by oxidative stress and endothelial dysfunction in hypercholesterolemia. Moreover, the effects of statins on sRAGE and oxidative stress contribute to the pleiotropic effects exhibited by these molecules.
Disclosure of interest: none declared.