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

6533b859fe1ef96bd12b7824

RESEARCH PRODUCT

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

Giovanni Davì Elisabetta Ferrante Loredana Bucciarelli Valentina Davì Maurizio Averna Giovanni Ciabattoni Davide Noto Caterina Pettinella Angelo B. Cefalù Francesca Santilli

subject

Male medicine.medical_specialty Settore MED/09 - Medicina Interna Statin medicine.drug_class Atorvastatin Hypercholesterolemia Receptor for Advanced Glycation End Products Free radicals Arginine Dinoprost Nitric Oxide medicine.disease_cause Biochemistry chemistry.chemical_compound Double-Blind Method Physiology (medical)Internal medicine Hyperlipidemia Atorvastatin medicine Humans Pyrroles Receptors Immunologic Endothelial dysfunction Pravastatin Chemistry Vascular disease Anticholesteremic Agents Statin nutritional and metabolic diseases Middle Aged Atherosclerosis medicine.disease ADMA Cross-Sectional Studies Hyperlipidemia Endocrinology Heptanoic Acids Oxidative stre Female lipids (amino acids peptides and proteins)Hydroxymethylglutaryl-CoA Reductase Inhibitors Nitric Oxide Synthase Asymmetric dimethylarginine Oxidative stress Pravastatin sRAGE medicine.drug

description

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-RAGE axis may bridge impairment of nitric oxide biosynthesis with oxidative stress. We measured in 60 hypercholesterolemic patients and 20 controls plasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) F(2alpha) 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. Plasma sRAGE was significantly lower, ADMA and urinary 8-iso-PGF(2alpha) were higher, in hypercholesterolemic versus normocholesterolemic patients. Patients on statin treatment with previous myocardial infarction had lower 8-iso-PGF(2alpha), higher sRAGE, and unchanged ADMA levels compared to subjects free of vascular disease. On multivariate regression analysis only 8-iso-PGF(2alpha) and ADMA predicted sRAGE levels. An 8-week treatment with either statin was associated with a significant reduction in urinary 8-iso-PGF(2alpha), whereas only atorvastatin raised sRAGE levels near to normal values, with no change in ADMA levels. sRAGE might serve as an endogenous protecting factor for accelerated atherosclerosis mediated by oxidative stress and endothelial dysfunction in hypercholesterolemia.

year	journal	country	edition	language
2007-11-01	Free Radical Biology and Medicine

https://doi.org/10.1016/j.freeradbiomed.2007.06.017