Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid.
Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.
Cangemi
Roberto
R
Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Rome 00161, Italy.
Angelico
Francesco
F
Loffredo
Lorenzo
L
Del Ben
Maria
M
Pignatelli
Pasquale
P
Martini
Alessandra
A
Violi
Francesco
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D003848:Deoxyguanine Nucleotides / Q000097:blood; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D008875:Middle Aged; D018384:Oxidative Stress
C521293:8-hydroxy-2'-deoxyguanosine 5'-triphosphate; D003848:Deoxyguanine Nucleotides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D001205:Ascorbic Acid