Decreased plasma soluble RAGE in patients with hypercholesterolemia: Effects of statins

Angelo Baldassare Cefalu', Maurizio Averna, Elisabetta Ferrante, Caterina Pettinella, Francesca Santilli, Loredana Bucciarelli, Giovanni Ciabattoni, Giovanni Davì, Davide Noto, Valentina Davi'

Risultato della ricerca: Articlepeer review

101 Citazioni (Scopus)

Abstract

The receptor for advanced glycation endproducts (RAGE) is overexpressed at sites of vascular pathology. A soluble RAGE isoform (sRAGE)neutralizes the ligand-mediated damage by acting as a decoy. We hypothesized that in hypercholesterolemia up-regulation of the ligand–RAGEaxis may bridge impairment of nitric oxide biosynthesis with oxidative stress. We measured in 60 hypercholesterolemic patients and 20 controlsplasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) F2α excretion, and plasma levels of asymmetric dimethylarginine (ADMA). Theeffects of two structurally different statins (pravastatin and atorvastatin) on these parameters were analyzed in 20 hypercholesterolemic subjectsfree of vascular disease. Plasma sRAGE was significantly lower, ADMA and urinary 8-iso-PGF2α were higher, in hypercholesterolemic versusnormocholesterolemic patients. Patients on statin treatment with previous myocardial infarction had lower 8-iso-PGF2α, higher sRAGE, andunchanged ADMA levels compared to subjects free of vascular disease. On multivariate regression analysis only 8-iso-PGF2α and ADMApredicted sRAGE levels. An 8-week treatment with either statin was associated with a significant reduction in urinary 8-iso-PGF2α, whereas onlyatorvastatin raised sRAGE levels near to normal values, with no change in ADMA levels. sRAGE might serve as an endogenous protecting factorfor accelerated atherosclerosis mediated by oxidative stress and endothelial dysfunction in hypercholesterolemia.
Lingua originaleEnglish
pagine (da-a)1255-1262
Numero di pagine8
RivistaFREE RADICAL BIOLOGY & MEDICINE
Volume43(9)
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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